Stem Cell Therapy

[munikur]

Hi forum,

Hope you are all doing well. We have two twin boys 8year diagnosed with ADHD/Autism, I am looking into getting Stem Cell Therapy for these kids. Anyone got this treatment for Autism/ADHD for your kids? can you please share your views on this.

Really appreciate it.

Thanks in advance
Raj

 

[Rodafina]

@munikur

What symptoms are present in your children that are in need of treatment?

What do you expect/hope stem cell therapy could do for your children?

 

[munikur]

Thanks for your response. One child is non-verbal, he is diagnosed with Autism. He get hyperactive and starts laughing loudly and the other child is ADHD diagnosed and he gets agitated, starts crying/yelling all the time, he is on medication but medication only works 70% of the time. He is verbal but only can speak few words.

My expectation from the treatment is that both will behave normally and I am hoping that they will start talking. They both go to ABA therapy about 24 hours a week, they have OT/ST but none of that is really helping.

 

[All-Rounder]

ABA is subject to many controversies, such as increased PTSD (post trauma stress disorder) symptomatology in participants.

From my reading, stem cell therapy for autism is considered safe, though it's still being studied.

I was very interested in it as it seems it can modify our social index and make it easier for us to behave in a more social and apt way. This also rises a lot of controversy because some people believe we should be able to be ourselves without expensive treatments and be able to live freely and learn our own way to cope with deficiency but honestly being autistic is a hardship and I desire for it to be easier and progress even in adulthood is very resistant in social and task completing situation which life in society heavily relies on. Additionally a lot of proposed cures have assaulted our history that were completely not helpful and downright ridiculous like some exotic milk or bread so the fact of a cure can be uncomfortable to hear about for some people.

 

[Tom]

I had Stem cell transplant for Leukemia but never heard of it before now as treatment for ASD. My initial survey suggests to me it is experimental and unproven. You may already be aware that many things, some claiming to be treatments or even cures, come along and claim to be effective but in long run are proven not to be, So I would be sceptical. Very sceptical in fact, until I saw mainstream medical proof and approval. ABA is main approach currently in use, in USA at least, and can be effective and is scientifcally well supported but is far from quick fix. It is used in school system up thru age 22. Not sure about after that age in post school situations where person needs support. ABA is not only tool of course, and treatment often, if not usually, requires a blend of many elements. CDC website has basic outline of other medically approved options.

Experimental or risky treatments, if medically approved are fine when facing otherwise terminal diseases like leukemia but something else when looking at mental disorders in children. I suggest you proceed very cautiously.

 

[Neonatal RRT]

Interesting. A therapy in development.

For more info, Google this. It is a PDF. International Child Neurology Association.

Position statement from the Advocacy Committee of the ICNA; Stem Cell Therapies in Autism Spectrum Disorders: Stem Cell Therapies in Autism Spectrum​

 

[Streetwise]

Hi forum,

Hope you are all doing well. We have two twin boys 8year diagnosed with ADHD/Autism, I am looking into getting Stem Cell Therapy for these kids. Anyone got this treatment for Autism/ADHD for your kids? can you please share your views on this.

Really appreciate it.

Thanks in advance
Raj

The autism community really dislikes ANYONE regarding autism as a disease ,infact it's neurotypicals that cause the evil in the world

 

[Neonatal RRT]

@munikur As someone with an Asperger's/ASD-1 variant, I can understand and mostly agree with the post made by @Streetwise. Since you are new to the community, do be aware that there is a vein of thinking within the autism community, more specifically those with ASD-1's that our variant can be an asset, despite some of the difficulties with dealing with the neurotypical world. Myself, and some others with Asperger's/ASD-1 variants have achieved success in life BECAUSE of our autism, not despite it. Overall, I like myself, despite some of difficulties. We recognize it is often neurotypicals that are responsible for much of evil in the world. Many of our caring parents exposed us to ABA therapies, with love. However, ABA is, essentially, trying to change who we are, which can, in some circumstances create a significant amount of mental stress and trauma. We all struggle with "masking", trying to hide who we are, every day, so we can carry on with interpersonal relationships and employment. It's horribly mentally exhausting to be "acting" and "in character" when out in public. Some of us, the stress is prohibitive, to the point of wanting to socially isolate. It's not good. Most of us wish we could simply be accepted for who we are, but the neurotypical world will not allow it. There can be a lot of mental baggage even having the "milder" variants of autism. As parents, do be sensitive to this.

Now, context and perspective is important to this discussion. Your children, from your description, suggests more "severe" variants, although that remains to be seen. The kids are still pretty young. A lot can happen. I am in the medical field, working at one the largest children's hospitals in the US, my team does work with autistic children on a daily basis, and do have some understanding of stem cell therapies. My son is currently a professor at a Detroit, Michigan area university and does quite a bit of stem cell research for biotech companies. That said, as a parent, I can understand your motivations for "trying something", even if it means enrolling in studies. Do understand that given that the protocols/methods for stem cell therapies in autism are not established. There is no "standard of care", as more study is needed. I certainly hope the best for your children.

 

[Cryptid]

Stem Cell Therapy has not been proven beyond any doubt to be ineffective in treating or "curing" neurodiverse conditions like ASDs and ADD/ADHD.

Read the complete and unedited article HERE .

How effective is stem cell therapy for autism?

So, is stem cell therapy effective? The answer to this is unknown.

Is ASD caused by genetic, immune dysfunction, or inflammatory stimuli? The answer to this is not clear and there’s a vast number of studies that argue different theories.

It is even more disturbing to consider these hypotheses because, for example, each person can experience bacterial or viral infections, or stress that can impact immune functioning and/or lead to inflammation but we’re not all on the spectrum. Therefore, we can’t say that factors which alter our immune functioning lead to the development of neurodevelopmental conditions.

However, the study by Riordan et al. (2019) proposes the influence of cytokines for the treatment of autism.The data proposed could be a point in a positive direction to answering whether stem cell therapy could potentially treat autism symptoms.

What is the success rate of stem cell therapy?

Unfortunately, there is no data to positively state the effectiveness of stem cell therapy for treating autism. As more research is developed in this field, there’s hope that more understanding of autism will arise, and perhaps an alternative form of treatment of autism symptoms can be developed. It is also worth noting the possibility of genetic markers that could help diagnose autism during pregnancy or during the prenatal development stage.
In summary

The studies highlighted in this article are simply preliminary assessments. Further research needs to be conducted in order to understand the potential of cell therapies for treating autism.

The findings of these studies vary in hypothesis and this makes generalization hard. Science has developed greatly over years, therefore, for those that believe in the potential of science and all that it could offer, there’s a reason to hope that stem cell therapy could potentially be used as treatment for autism in the near future.

References:

Biehl, J. K., & Russell, B. (2009). Introduction to stem cell therapy. The Journal of cardiovascular nursing, 24(2), 98–105. Introduction to Stem Cell Therapy : Journal of Cardiovascular Nursing

Price, J.(2020). Cell therapy approaches to autism: a review of clinical trial data. Molecular Autism, 11, 37 . Cell therapy approaches to autism: a review of clinical trial data - Molecular Autism

Stem Cell Program Research | Boston Children's Hospital

Thermo Fisher Scientific. An Overview of Pluripotent and Multipotent Stem Cell Targets. https://www.thermofisher.com/za/en/...luripotent-multipotent-stem-cell-targets.html

Yu, Z., Han, B. (2016). Advantages and limitations of the parthenogenetic embryonic stem cells in cell therapy. Journal of Reproduction and Contraception, 27 (2), Issue 2, 118-124. https://doi.org/10.7669/j.issn.1001-7844.2016.02.0118

 

[GrownupGirl]

I'm an adult woman who is late diagnosed with "mild" autism, so my thoughts or feelings about this situation clearly don't matter.

 

[All-Rounder]

Stem cell therapy in autism: recent insights
An article from 2018.


"Fetal stem cells

FSCs have the ability to secrete various neurotrophic and immunomodulatory factors that promote neuronal growth and suppress the action of proinflammatory cytokines that make them a potential candidate for treating ASDs and various neurodegenerative diseases.

A clinical trial in younger human Parkinson’s patients also showed promising results when dopamine neurons from fetal neural tissues were transplanted.36 An open-labeled clinical trial that examined the safety and efficacy of FSCs in autistic children revealed no adverse events and a significant difference in the improvement of autistic symptoms (detailed in Stem cells and autism: animal models section).


Bone marrow-derived stem cells
Mesenchymal stem cells (MSCs)

Different mechanisms were hypothesized for using MSCs for treating ASDs that include inducing plasticity, secretion of anti-inflammatory and survival-promoting factors, and engrafting into neural network.45

Also, in vivo, in different animal models of neurodegeneration, MSCs exert neuroprotection mainly by secretion of various neurotrophic and immunomodulatory factors, thus facilitating the recruitment of endogenous stem cells to promote regeneration and by downregulating T cells, B cells, and NK cells of immune system.46 Owing to these properties, MSCs were highly preferred candidates for clinical trials for various neurologic diseases. Clinical trials using MSCs are ongoing for diseases like multiple sclerosis (MS), stroke, Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), and systemic autoimmune diseases.47 For ASDs, several studies using stem cells have been conducted in humans (detailed in Stem cells and autism: animal models section); a study by Lv et al analyzed the safety and efficacy of using human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism.48 They reported safe and statistically significant improvements in the Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale, and Aberrant Behavior Checklist (ABC) in the children treated combinedly with CBMNCs and UCMSCs when compared to the control group.


Adipo-stem cells

Along with being multipotent, ASCs secrete various trophic factors and are immunosuppressive and hypoimmunogenic, making them an attractive candidate for cellular therapies. ASCs have been used in various clinical trials targeting a wide range of indications ranging from immune disorders, myocardial infarction, bone defects, and neurodegenerative diseases. Although no reports have been found on the use of ASCs for treating ASDs, ASCs have been proven effective in other neurologic preclinical models, as in the mouse model of middle cerebral artery occlusion, human ASCs partially rescue the stroke syndromes by forming new neurons and blood vessels and increasing the viability of endogenous neurons.


Umbilical cord- and amniotic fluid-derived stem cells

These cells from perinatal, extraembryonic tissue have potential for future applications in ASDs.22 There are no ethical controversy and risk of teratoma formation, and they could also be used for autologous transplantation after banking in later stages of life.55


NSCs

The NSCs that can be extracted from two major regions of the brain, namely, the subventricular zone of lateral ventricles and subgranular zone of hippocampus, can be cultured.57,58 The culture-expanded NSCs are multipotent, have the ability to differentiate into various neuronal cell types, secrete neurotrophic factors, integrate into neural tissue, maintain homeostasis, and are neuroprotective, making them an ideal candidate for treating ASDs. Indeed, impairments in excitatory and inhibitory cortical neurons lead to minicolumn structure abnormalities in ASDs.56 Synaptic-related genes show multiple rare variants in some ASD subjects.59 Given that, transplantation of NSCs could be effective in ASDs, as transplanted cells can promote neural tissue repair and homeostasis through integration in damaged areas and secretion of factors that enhance brain repair and plasticity.60 The definitive use of NSCs for clinical applications in neurodegenerative diseases still requires addressing some critical issues: autologous reliable source of sufficient amount of stem cells needs to be identified; post-transplanted neural plasticity and differentiation, if any, must be further defined.60 However, though NSCs have been used in various preclinical and clinical studies against different neurologic conditions like PD, HD, AD, amyotrophic lateral sclerosis (ALS), MS, stroke, and spinal cord injury (SCI), the outcome is not definitive as expected and is hindered by several points to be further elucidated: the absence of homogenous cell population, stability, and long-term survival of neurons after transplantation.61,62

Different methods have been tried to enhance the capabilities of NSCs, like immortalizing the NSCs by gene manipulation techniques to create a homogenous, long-surviving cell that is capable of differentiating into neurons and glial cells when transplanted into normal or damaged brain.58


Hematopoietic stem cells (HSCs)

HSCs are mainly resident in bone marrow and also in blood and umbilical cord.63 Self-renewal, multipotency, and homing/mobility activities are very high. This type of stem cells is able to differentiate in myeloid and lymphoid lineages. Their paracrine activity, releasing bioactive molecules, and their ability to quickly traffic to the site of inflammation gained them a lot of attention for their use in ASD therapy.63 Several clinical trials have been performed with the use of CD34+ stem cells in autism (detailed in Stem cells and autism: animal models section).


iPSCs: the new frontier for cell therapy

There are several in vivo studies that prove the efficiency of iPSCs in treating neurodegenerative disorders, cardiovascular disease, and sickle cell anemia. For example, in contusive SCI model in nonobese diabetic severe combined immunodeficient mice, injection of neurospheres derived from human iPSCs leads to recovery of locomotor function without formation of any tumors.67 The differentiation capabilities of injected neurospheres into neurons, astrocytes, and oligodendrocytes along with induction of angiogenesis, axonal regeneration, and local-circuitry reconstruction may contribute to the recovery in SCI model.67 When autologous iPSCs-derived dopamine neurons were transplanted in PD model of cynomolgus monkey, the neurons engraft and survive for prolonged time of 2 years leading to improvement in the motor function in the nonhuman primate model.68 iPSCs have also been used effectively against HD and ALS by their capability to differentiate into desired neuronal lineages.

iPSC applications gain much attention also for autism research.73 Successful reprogramming of peripheral blood-derived mononuclear cells from autistic child into iPSCs has been performed by transgene-free delivery system.74 Customized iPSCs will help in elucidating the pathogenic mechanisms of ASDs,75 also for neuronal differentiation and maturation.76

Indeed, iPSC-derived neurons from autistic subjects show aberrant cation channels expression, voltage-gated currents, and changes in synaptic functions.77,78 Autistic patient-derived stem cells display an altered developmental neuronal phenotype: alteration in cell bodies, branched neurites, and motility compared with those derived from controls.79 Using iPSCs to generate three-dimensional models of neurons and brain structures could also be useful to model autism pathophysiology.

 

[All-Rounder]

Animal models

Human MSCs were intracerebroventricularly transplanted (50,000 cells/µL) in BTBR mice.82 Cell therapy improved repetitive behaviors in transplanted mice by means of decreasing digging and self-grooming duration and increasing the latency between two consecutive events. Cell-transplanted mice also displayed decreasing in cognitive rigidity as measured by water T-maze test. To note, social behavior was also improved: transplanted BTBR mice reported better social approach and social novelty preference with respect to nontransplanted BTBR mice.82 By a cellular point of view, hMSCs improved hippocampal neurogenesis (increasing of Ki-67 and DCX markers) and increased BDNF levels; after 6 weeks post-transplantation, hMSCs were found to be located close to the wall of the dorsal third ventricle. In the same mouse model, hMSC transplantation (50,000 cells/µL into the cerebral lateral ventricle) showed long-term beneficial effects in ameliorating autistic-like symptoms.83 Social behaviors were improved and stereotypic behaviors were reduced at 6 months posttransplantation. Another human stem cell type, the ASCs (50,000 cells/µL, intraventricularly), was successfully used in valproic acid (VPA)-induced autism mouse model.84 Transplanted mice displayed increased motor coordination (as measured by open-field test) and social behaviors and decreased anxiety. Human ASCs were responsible to increase the phosphatase and tensin homolog, VEGF, IL-10 expression, and p-AKT/AKT ratio in the brains of VPA mice.84 Mouse-derived MSCs were used in VPA-induced autism model, resulting in increasing neurogenesis and promoting maturation of newly formed neurons in the dentate gyrus 2 months after transplantation.85 MSCs were expanded in culture for up to 20 passages and immunophenotyped for mesenchymal specific markers. Then thousands of MSCs in 5 µL MSC were transplanted into the right lateral ventricle. Deficits in cognitive and social behaviors were also improved after 2 weeks posttransplantation.85

Beyond stem cell therapy as valuable tool for treating autism, stem cells also offer the possibility for in-depth study of ASD pathology. Offspring of immune-activated mothers (maternal immune activation autism model) develop preferential myeloid lineage potential and altered differentiation of HSCs.86 The importance of this work reflects that immune changes during maternal life could confer alterations in stem cells lineage through the entire life of offspring.


Stem cells and autism: clinical trials

Sharma et al conducted an open-label proof-of-concept study on the use of autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in 32 subjects (median age at intervention 10.5 years, male:female 3:1) with confirmed diagnosis of autism.88 The protocol included intrathecal cellular therapy followed by occupational therapy, sensory integrative approach, speech therapy, psychological intervention, and specific dietary recommendations. Mononuclear cell fraction is a heterogeneous mixture consisting of endothelial progenitors, HSCs and MSCs, and multipotent adult progenitor cells. These cells were separated from the aspirate of bone marrow, counted by CD34+ marker and checked for viability. On the same day, the cells were intrathecally injected and methyl prednisolone was given intravenously to enhance survival of the injected cells. Long-term adverse events were monitored to establish the safety of stem cell transplantation. Minor adverse events (vomiting, nausea, pain at side of injection, or aspiration) were present. These events were reported to be procedure-related and not cellular transplantation-related issues. Minimal increase in hyperactivity was recorded as a major adverse event related to cell procedure, along with three patients developing seizures. After cellular therapy, Indian Scale for Assessment of Autism (ISAA) indicated improvements in the domains of social relationships and reciprocity (improved eye contact, social smile, and reaching out to others), cognitive aspects (attention, concentration, and time of response), and also in speech and language patterns (reduction in echolalic speech, engaging in stereotyped repetitive use of language, production of infantile squeals or unusual noises, inability to initiate or sustain conversation with others, inability to grasp the pragmatics of the conversation, and speech regression). Decrease in inappropriate emotional responses, exaggerated emotions, engaging in self-stimulating emotions, and getting excited or agitated for no apparent reason was recorded. CGI scale scored changes in the severity of the disease, overall improvement, and the efficacy of the treatment. Interestingly, functional neuroimaging, by the means of positron emission tomography (PET) scan, showed increased 18F-fluorodeoxyglucose (18F-FDG) uptake in the areas of frontal lobe, cerebellum, amygdala, hippocampus, parahippocampus, and mesial temporal lobe after 6 months of cellular therapy. Hypoperfusion has been recently demonstrated in key brain areas of ASD subjects.89 Hypometabolic areas before cell transplantation showed increased metabolism after cellular delivery, probably due to improved oxygenation and functioning of the damaged neurons. As limitations, authors report the small sample size, and the absence of randomization and a control group.88

Most recently, Sharma et al performed this type of cellular treatment on a male autistic adult (25 years old).90 Autologous BMMNCs were intrathecally transplanted. No major adverse events were seen. After 6 months of cellular therapy, improvements in concentration, sitting tolerance, attention, sleep, eye contact, social interactions, and memory were reported, as measured by ISAA, CARS, and Functional Independence Measure scores before and after cellular treatment. Six months posttherapy, 18F-FDG PET scan showed improvements in brain hypometabolism."