Future/Asha Ek Hope in the treatment of ALS/MND
- Stem Cell Therapy
- Gene therapy trials
- Basic research exploring the genetic origin of ALS
- Biomarkers for ALS
- PET-CT scan for ALS
- Non invasive EMG for ALS
Stem cell therapy is being explored extensively for MND/ALS. Experimental studies in animals have shown promising results. Some of the clinical studies in human beings have shown preliminary results of beneficial effect in the disease progression.
Stem cells are divided into two broad groups:
- Allogenic (Stem cells taken from outside)
- Autologous (Stem cells taken from the patient itself)
Autologous stem cells are extremely safe to use because they are from the same patient. They are easily available and have no ethical issues. Autologous stem cells are divided into:
- bone marrow derived stem cells
- adipose (fat) derived stem cells
- peripheral blood stem cells.
Recent systematic review and meta-analysis of studies showed the safety and efficacy of stem cell therapy in preclinical and clinical studies.
In India, a pilot study of autologous bone marrow derived stem cell in patients with ALS was published in the journal of Neurology India. . This pilot study concluded autologous bone marrow derived stem cell therapy is safe and feasible and suggested stabilization of disease in ALS patients .
Another Indian controlled study of ALS patients was published in American Journal of Stem Cells. Patients underwent autologous bone marrow mononuclear cell transplantation in addition to standard rehabilitation , Riluzole and Lithium. Overall stem cell therapy group survived longer. The result showed that the disease had slowed down in people undergoing stem cell therapy in comparison to the control group. Also some young patients in early stage of disease showed halted progression.
You should consider all the factors before choosing stem cell therapy. Patients with respiratory involvement or advanced stages may not benefit from the current protocol. Stem cells may be used in slowing down/ halting of disease progression in certain subset of patients We recommend that you should gather all the information about the stem cell centre, doctors, cell type, route of administration, safety, cell protocol and previous results of that centre. This will empower you to make an informed choice.
- NurOwn® technology takes MSCs and, by growing them in proprietary conditions, converts them into biological factories secreting a variety of neurotrophic factors (NTFs).
- NTFs are growth factors known to support the survival of neurons in a variety of conditions,
- Over 60 patients with amyotrophic lateral sclerosis (ALS) have been treated with NurOwn® in clinical trials conducted in the United States and Israel,
- establishing an excellent safety and tolerability profile and demonstrating promising signs of efficacy.
Neuralstem Cell Therapy
- U.S.: FDA-approved multi-center Phase II NSI-566/ALS clinical trial, with significant increase in dosing, concluded in 1Q15.
- Larger, controlled, registration directed NSI-566/ALS clinical trial expected to commence in 2016
- Mechanism of Action: Rebuilding neural circuitry
- Route of Administration: Direct injections of its NSI-566 human spinal cord stem cells (HSSCs) into the gray matter of the patient’s spinal cord.
- Neuralstem cell therapy platform is the delivery of the cells directly into the gray matter of the spinal cord, where they can protect and integrate with the patient’s spinal cord neurons.
- Nuedexta drug – psuedobulbar affect of ALS
- Edaravone drug – recently approved in Japan for neuroprotection in ALS
- Cerebrolysin drug– for neuroprotection
- Genervon GM604 – for TDP – 43 aggregates
- Ibudilast – antiinflammatory
- Retigabine – reduce hyperexcitability of neurons
- FDA approved in October 2010
- dextromethorphan hydrobromide/quinidine sulfate capsules in a fixed-dose combination for oral use only in patients with pseudobulbar affect.
- Ongoing trials to determine whether Nuedexta is effective in the treatment of impaired speech, swallowing, and saliva control associated with ALS.
- Approximately 60 eligible subjects with ALS will be recruited from multiple centers in the US
Edaravone & Cerebrolysin:-
- IV injections given over a long period
- Cannot be given to elderly people and kidney disorder
- Phase 2A clinical trial indicated that GM604 has the ability to reduce the formation of random protein aggregates, to modulate protein biomarkers and can bring the TDP-43 protein back to their normal ranges
- Ibudilast (development codes: AV-411 or MN-166)
- antiinflammatory drug used mainly in Japan,
- acts as a phosphodiesterase inhibitor, inhibiting the PDE-4 subtype
- used in the treatment of asthma
- may also be useful in the treatment of multiple sclerosis.
- Harvard stem cell scientists have discovered that a recently approved medication Retigabine for epilepsy might be a meaningful treatment for (ALS).
- r educed the cells’ hyperexcitability.
|Sr. No.||Title of the research||Status of the trial||Organization conducting the research|
|1||Ibudilast (MN-166) in Subjects with Amyotrophic Lateral Sclerosis (ALS)||Recruiting||Carolinas Healthcare System, Dept. of Neurology Charlotte, North Carolina, United States,|
|2||Olanzapine for the Treatment of Appetite Loss in Amyotrophic Lateral Sclerosis (ALS)||Recruiting||Charite University, Berlin, Germany|
|3||Mexiletine for the Treatment of Muscle Cramps in ALS||Recruiting||University of California, Davis ALS Association|
|4||Intravenous Injection of Adipose Derived Mesenchymal Stem Cell for ALS||Recruiting||Royan Institute, Iran, Islamic Republic|
|5||Evaluation of Metabolomic Analysis in Early Diagnosis of ALS (METABALS)||Recruiting||University Hospital, Tours|
|6||A Pilot Study of Inosine in ALS||Recruiting||Massachusetts General Hospital, United States, Massachusetts|
|7||A Clinical Trial of Safety and Efficacy of Fasudil in Subjects With Amyotrophic Lateral Sclerosis [ALS]||Recruiting||Peking University Third Hospital, Beijing, China,|
|8||F 18 T807 Tau PET Imaging in Familial Amyotrophic Lateral Sclerosis (T807 ALS)||Recruiting||Washington University School of Medicine United States, Missouri|
|9||The Objective is to Compare the Efficacy and Safety of Masitinib in Combination With Riluzole in the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis [ALS]||Recruiting||Madrid, Spain|
|10||A Phase 3, Multi-National, Double-Blind, Randomized, Placebo-Controlled, Stratified, Parallel Group, Study to Evaluate the Safety, Tolerability and Efficacy of Tirasemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)||Recruiting||Carol and Frank Morsini Centre for Advanced Health Care – University of South Florida|
|11||A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS)||Recruiting||Massachusetts General Hospital, Neurological Clinical Research Institute, Boston, UNITED STATES|
|12||Developing a Discrimination Model to Diagnose ALS Using Advanced MRI Techniques||Recruiting||University of Michigan Hospital, Ann Arbor, Michigan, UNITED STATES|
|13||Paired Stimulation to Increase Cortical Transmission to Hand Muscles: Pilot Study||Recruiting||J. Peters VA Medical Center, Bronx, New York, UNITED STATES|
|14||Initiation of Long-term Home Non-invasive Ventilation in ALS Using the iVAPS Mode During a Daytime Trial||Recruiting||Montreal Chest Institute, Montreal, Quebe, CANADA|
|15||A Phase 2 Pharmacodyamic study of Ezogabine on neuronal excitability in Amyotrophic Lateral Sclerosis||Recruiting||Massachusetts General Hospital – Neurological Clinical Research Institute (MGH-NCRI)|
- In a transgenic ALS mouse model expressing mutant SOD1G93A protein, silencing the SOD1 gene prolongs survival.
University of Tokyo
- developed an adeno-associated virus serotype 9 (AAV9) vector that would enable gene delivery only to the neurons of mouse brain and spinal cord.
- When this vector was given by intravenous injection into the ALS model mice , the researchers succeeded for the first time in stopping the degeneration and loss of motor neurons and the progression of symptoms
- Diagnostic biomarkers are any small molecules that can be detected in the blood or cerebrospinal fluid (CSF) and are associated with a disease.
- enable earlier and accurate diagnosis of ALS, with a greater chance for earlier treatment to alter the disease course.
- possible to measure the effectiveness of different drug treatments in clinical trials.
- A set of 19 proteins has shown promise as a biomarker panel for ALS