giovedì 1 ottobre 2009

FDA green lights stem-cell

clinical trial for Lou Gehrig’s disease

2 commenti:

Fabio e Fabrizio ha detto...

FDA green lights stem-cell clinical trial for Lou Gehrig’s disease
The Maryland company NeuralStem has the U.S. Food and Drug Administration’s permission to test its spinal cord stem cells in twelve patients with amyotrophic lateral sclerosis. The approval comes a month after the FDA placed Geron’s planned clinical trial on hold for a second time. NeuralStem’s trial had also previously been placed on hold by the FDA in February before receiving the go-ahead in September.

Though both trials involve placing cells into the spinal cord, NeuralStem’s product is made of cultured neural stem cells derived from a single 8-week fetus; Geron’s product, intended to treat spinal cord injury, is derived from embryonic stem cells that have been differentiated into precursors of neuron-support cells.

“This is certainly the first stem-cell approach for ALS,” says Lucie Bruijn, a scientist at the ALS Association, a patient group that also funds relevant research. Most other approaches for treating ALS are small molecule drugs, she says, and she’s not aware of other cell therapy or other invasive approaches entering human testing in the near future.

ALS has not funded NeuralStem’s work directly, Bruijn says, but has advised the company and funded academic scientists who’ve been involved with the company.

NeuralStem’s chief scientific officer Karl Johe says tests of large animal models show that the transplanted cells exert a neuroprotective effect over motor neurons, but it’s not entirely clear how. Earlier this year, Neuralstem and collaborators published results in a rat model of ALS showing that transplanted cells could develop into interneurons that formed synapses with the rats’ motor neurons.

However, Johe emphasized that the upcoming trial will assess safety rather than efficacy. The first few patients selected for the procedure will be those who are no longer able to walk. Because the injected cells protect rather than replace motor neurons, these sicker patients are less likely to benefit from treatment, but they are less able to lose function if something goes wrong. Cells will be injected only on one side of the spinal cord in order to minimize the number of injections into the spinal cord. Only one patient will be injected each month, so that researchers can monitor for effects over a longer period. Eventually, Johe says, the goal is to be able to inject cells in both lower and upper regions of the spinal cord in healthier patients, and see if the injections can keep motor neurons healthy.

The trial is expected to take place at Emory University in Atlanta, Georgia. Though the FDA is allowing the trial to go forward, the university’s patient-safety board will also need to approve the trial before it can proceed. Johe declined to say when that would be but said discussions were well underway.

Other companies using neural cells include ReNeuron, which received permission from UK authorities this January to start clinical trials for stroke. Its cell product is made from genetically modified cultures of neural stem cells, also of fetal origin.

StemCells Inc is conducting trials in Batten’s disease, a neurodegenerative disease that strikes children, and recently received approval for a clinical trial for a similar disease. It also uses neural stem cells from material originally derived from fetuses and has recently published results showing that its cell product delayed some symptoms of the disease by about three weeks.

As with human embryonic stem cells, the patent situation for neural stem cells is contentious. In a pair of dueling press releases this May, NeuralStem and Stem Cells Inc both claimed key intellectual property on these cells.

Fabio e Fabrizio ha detto...

We have just read, not without some interest, the NeuralStem communicate. The trial is presented as if it were the first clinical study with stem cells in ALS (“This is the first stem-cell approach for ALS” says Lucie Bruijin). However, this needs to be rectified as we conducted two phase 1 clinical trials one in 2001 (Mazzini et al., 2008)) and the other in 2007 (Mazzini L et al., 2009). The trials were approved respectively by the regional Ethical Committee and by the Italian Institute of Health and by the and were designed to test the safety and the feasibility of mesenchymal stem cell transplantation into the spinal cord of ALS patients.
MSC were isolated from patients’ bone marrow, in vitro expanded for 3-4 passages and evaluated for quality control as requested by national rules on advanced therapies. In neither of our trials were there any immediate or delayed transplant related toxicities. Stem cells were transplanted into the spinal cord at the thoracic levels with a surgical approach. Clinical, laboratory, and radiographic evaluations of the patients showed no serious transplant related adverse events. Magnetic resonance images (MRI) showed no structural changes (including tumor formation) in either the brain or the spinal cord.
Furthermore, we also demonstrated that expanded MSCs can survive and migrate after transplantation in the lumbar spinal cord of SOD1-G93A mice, where they prevent astrogliosis and microglial activation and delay the ALS-related decrease in the number of motor neurons, resulting in an amelioration of motor performance (Vercelli A et al., 2008 ). Therefore we concluded that MSCs represent a good source of stem cells for future ALS cell based clinical trials.
Thus, the NeuralStem trial, as it appears, shows this experimental design to be no different to our studies except for the cell type: neural stem cell derived from a 8-week fetus.

Letizia Mazzini, MD ALS Centre, Dpt of Neurology ,Eastern Piedmont University Maggiore della Carità Hospital Novara, Italy

Franca Fagioli, MD Stem Cell Transplantation and Cellular Therapy Unit Pediatric Onco-Hematology Department Regina Margherita Children’s Hospital Torino. Italy


1.Mazzini, L. & Mareschi, K.& Ferrero, I.& Vassallo, E.& Oliveri, G.& Nasuelli, N.& Oggioni, GD.& Testa, L.& Fagioli F. Stem cell treatment in Amyotrophic Lateral Sclerosis. Journal of the Neurological Sciences 265 (2008) 78–83

2. Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, Mareschi K, Testa L, Stecco A, Tarletti R, Miglioretti M, Fava E, Nasuelli N, Cisari C, Massara M, Vercelli R, Oggioni GD, Carriero A, Cantello R, Monaco F, Fagioli F Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.Exp Neurol. 2009 Aug 13. [Epub ahead of print]

3. Alessandro Vercelli, Oana M Mereuta, MD; Diego Garbossa, MD; Giuseppe Muraca; Katia Mareschi; Deborah Rustichelli; Ivana Ferrero; Letizia Mazzini, MD; Enrico Madon, MD; Franca Fagioli, MD Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis
Neurobiology of disease. 31 (2008) 395–405