Abstract Details

Title Interim analysis of 12 patients with amyotrophic lateral sclerosis (ALS) treated with autologous differentiated mesenchymal stem cells: Preliminary data of a Phase I/II clinical trial

Topic Anterior Horn

Presentation(s) (-)

Poster/Presentation
Number 008

Objective

Background A previous study from our group at Hadassah has shown the safety of IV/IT administration of unmodified MSC in ALS patients. MSC-NTF demonstrated neuroprotective effects in various animal models of neurodegenerative diseases, including ALS.

Design/Methods This Phase I/II clinical study will include upon completion 24 ALS patients. Twelve participants have already been recruited. MSC were isolated from the patients’ own bone marrow, expanded ex-vivo and induced to differentiate into MSC-NTF secreting GDNF and BDNF. Autologous MSC-NTF cells were transplanted, by IM (at 24 sites:200,000 cells per site) or IT (1x10⁶ cells/kg) injections to patients with early (ALSFRS score of >30; n=6) or advanced ALS (ALSFRS: 15-30; n=6), respectively. Patients were followed up clinically on a monthly basis for a pre-treatment period of 3 months and for 6 months post-transplantation. Respiratory function tests, 3D-MRI of the muscles and compound muscle action potential amplitudes at 3 sites were used as additional surrogate markers of disease activity.

Results During the six-month follow-up of the transplanted patients, no serious treatment-related adverse events were observed, indicating a short-term treatment safety. The clinical follow-up of the patients revealed initial indications of beneficial clinical effects in the MSC-NTF transplanted patients, as evidenced by a significant change in the rate of clinical progression (ALSFRS), in the respiratory function, in electrophysiology and in the 3D-MRI volumetric evaluation of the muscles, as compared to the 3 months preceding the treatment.

Conclusions Preliminary results of our ALS trial with autologous IM/IT MSC-NTF transplantation indicate that the used treatment protocols appear to be safe. Further analysis of the accumulated data and longer follow up of the participating patients are needed to confirm these observations.

Authors/Disclosures
Dimitrios Karussis, MD, PhD (Hadassah HMO)	Prof. Karussis has nothing to disclose.
Sandra Vanotti, MD (Biogen Idec)	No disclosure on file
Panayiota Petrou	No disclosure on file
	No disclosure on file
Marc Gotkine, MD (Hadassa University Hospital)	No disclosure on file
Zohar Argov, MD (Hadassah Hebrew University Medical Center)	No disclosure on file
Adi Vaknin-Dembinsky, MD	No disclosure on file
Ibrahim Kassis, PhD (Hadassah)	No disclosure on file
Tamir S. Ben-Hur, MD, PhD (Hadassah Hebrew University Medical Center)	The institution of Dr. Ben-Hur has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MAPI Pharma. The institution of Dr. Ben-Hur has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kadimastem. The institution of Dr. Ben-Hur has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sipnose. The institution of Dr. Ben-Hur has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regenera Pharma. The institution of Dr. Ben-Hur has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medasense. Dr. Ben-Hur has received stock or an ownership interest from Sipnose. Dr. Ben-Hur has received stock or an ownership interest from Kadimastem. Dr. Ben-Hur has received stock or an ownership interest from MAPI Pharma. Dr. Ben-Hur has received intellectual property interests from a discovery or technology relating to health care.
Eldad Melamed, MD (Rabin Medical Ctr Beilinson Campus)	No disclosure on file
Paolo Curatolo (Hotelplan)	No disclosure on file

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