To further its mission, Fast Forward held a ‘think tank’ on December 3 at Harvard Medical School in Boston, in collaboration with Harvard’s NeuroDiscovery Center, including representatives from venture capital firms, voluntary health and patient advocacy groups, pharmaceutical and biotechnology companies, and university-based research scientists to share information and ideas around this issue and ways to overcome them.
One big barrier to getting new drugs to treat and prevent neuro-degeneration in MS is the cost, which can stop companies from taking on financial risks early in the development of a potential therapy. It takes an average of 16 years, and up to $1.5 billion, to bring a promising new drug to market – and only one out of every 10,000 agents make it that far.
Sha Mi, PhD, Principal Investigator at Biogen Idec, shared lab work her company is doing to develop an antibody that blocks a molecule called LINGO to enhance nervous system repair. Marie Filbin, PhD (Hunter College, City University of New York) summarized some of her team’s work on some potential new targets for stopping ongoing brain injury in MS, and their identification of several compounds that can stop that injury – at least in the lab. The challenge that Dr. Filbin and other basic researchers face is that they are not equipped to do the vast number of medicinal chemistry tests and steps needed to take a promising lab compound and turn it into a commercial drug, such as what Biogen Idec hopes to do with the LINGO antibody.
Peter Stys, MD (University of Calgary) described some important discoveries related to MS nerve damage and some commonalities he sees to the pathology of stroke that are opening up new possibilities for intervention. Phil De Jager, MD, PhD (Harvard Medical School) summarized recent progress in identifying genes that make people susceptible to MS, and a major push the International MS Genetics Consortium hopes to make over the next year to identify all of the genes that contribute to MS, which will open the door to understanding its cause and ways to stop the disease.
The think tank is one example of Fast Forward’s strategies: to create alliances and collaborations – even among competitors – that will nourish and speed drug development efforts. “This is about collaborations, about conversations, about getting people to play in the sandbox together in a way where everyone wins,” said Timothy Coetzee, PhD, Executive Director of Fast Forward.
Barely a year old, Fast Forward funded its first research project on December 23, 2008. The award was $1 million to the young biotech firm, Apitope, to conduct a proof of principle clinical trial on a promising new vaccine, ATX-MS-1467, designed to target and redirect immune response in MS. On January 13, Apitope further announced that it also entered into a licensing agreement with Merck Serono to collaborate on the development and commercialization of the ATX-MS-1467 therapy. This agreement is welcome news to the Society because it provides important external validation of the rigorous scientific and business review process that Fast Forward employed in making its decision. The Apitope/Merck Serono partnership assures that funding will be in place to take ATX- MS-1467 to the next research phase if the proof of principle trial yields positive results.
Three recently published reports focus in new findings on magnetic resonance imaging (MRI) – the preferred imaging method for MS – and diffusion tensor imaging (DTI), a promising new MRI-based technique.
Study 1: Robert Naismith, MD (Washington University, St. Louis) and colleagues report the first evidence that DTI may help to predict the functional effects of damage in people with MS. DTI measures the random flow of water in tissues. Water normally flows parallel to nerve fiber tracts, but the rate of diffusion and direction of flow are altered by MS damage.
Dr. Naismith’s team used DTI and tests of visual health to examine the optic nerves of 12 people with recent optic neuritis (ON, inflammation of the optic nerve, a common MS manifestation); 28 people with a history of ON; and 12 healthy controls. Water diffusion decreased significantly in acute ON, and correlated with decreased sensitivity to visual contrast one month and three months later. In people with a history of ON, changes in water diffusion correlated with later, lower scores on several visual health tests. The team comments that these results show that DTI deserves further study as a potential predictor of clinical outcomes, and are expanding this approach to assess MS attacks in the brain and spinal cord.
Study 2: Darrin T. Okuda, MD, Daniel Pelletier, MD, and colleagues (University of California, San Francisco) examined the role of MRI in predicting MS among people who have no symptoms of MS. People are considered at high risk for MS if they experience clinically isolated syndrome (a first neurologic episode that lasts at least 24 hours, and is caused by inflammation/demyelination in one or more sites in the central nervous system). Clinical trials have shown that early treatment of CIS can delay the second clinical event, and therefore delay the diagnosis of MS. Dr. Okuda examined 44 people who had MRI scans taken for various reasons; all scans showed abnormalities suggestive of MS, but none had clinical symptoms. Thirty of these people were followed clinically, and 10 developed CIS or MS after a median time of 5.4 years. The authors note that studies in a larger cohort are needed to ascertain whether certain features of MRI alone can predict MS onset.
In an accompanying editorial, Dennis Bourdette, MD, and Jack Simon, MD, PhD (Oregon Health & Science University, Portland) comment, “Despite the usefulness of MRI, the patient’s symptoms remain the bedrock on which we base the diagnosis of MS.” They add, however, that this study may help to develop the evaluation of people who only show MRI signs of MS. For example, neuropsychological evaluations may reveal cognitive impairments suggestive of MS, which may open the door to an earlier diagnosis of MS and earlier treatment.
Study 3: Martin Daumer, PhD, Scientific Director of the Sylvia Lawry Centre for MS Research, and colleagues including George Ebers, MD (Oxford University, UK), used the center’s extensive data collection to study the role of MRI in clinical trials. The Sylvia Lawry Centre, which was launched by the MS International Federation with co-funding from the Society and others, has built a large-scale database of patient information from over 20,000 patients from the placebo groups of major clinical trials conducted over the last 20 years.
Dr. Daumer’s team used information from 31 studies of people with relapsing-remitting and secondary-progressive MS to assess the relationship between T2 lesion load and disability progression (T2-weighted MRI scans provide information about disease burden or the total amount of lesion area), as well as gadolinium enhancement and relapses (gadolinium-enhanced MRI highlights areas of breakdown in the blood-brain barrier that indicate inflammation). Gadolinium enhancement did not help to predict future relapses in a group of 170 people and T2 changes did not predict future disability change in 223 people with relapsing remitting MS. T2 changes did have a small impact on predicting disability in 355 people with secondary-progressive MS.
The authors say that these results call into question the usefulness of MRI in measuring outcomes in clinical trials. However, “This study does not address the correlation between MRI measures and long-term outcomes, which is what we are primarily interested in when we treat people with MS,” says John Richert, MD, Executive Vice President of Research & Clinical Programs at the Society. “But it highlights a need for advanced technologies that can clarify damage or predict disease course.”
Researchers Report Good Results from Small Study of Stem Cell Therapy to “Reboot” Immune System in MS
One of several studies testing potential benefits of giving patients their own blood or bone marrow stem cells
Dr. Richard Burt and colleagues at Northwestern University report on the safety and benefits from an early phase study of experimental transplantation of individuals’ own blood stem cells to turn off the immune attacks in MS. Unlike some of the previous studies of this procedure, this one involved 21 people with relapsing-remitting disease, rather than people with later stage, progressive disease.
In this uncontrolled trial, they found that the procedure was relatively safe, and after an average of 37 months, none had progressed and a significant portion experienced a reversal of at least 1 point on their disability (EDSS) scores, and 76% remained free from relapses. As pointed out by the investigators, it will take larger-scale, controlled trials to determine whether this expensive, potentially risky procedure is superior to other approved treatment options. Controlled trials of this procedure are now recruiting participants.
Autologous hematopoetic stem cell transplantation is similar to bone marrow transplantation to treat cancer, except that it uses the patients’ own blood or bone marrow stem cells. In treating MS, the procedure generally involves removing, from the blood stream, a person’s cells that are capable of regenerating into new immune cells. These “stem cells” are stored, and the rest of the immune cells are destroyed by various chemotherapy or other regimens. Then the stored stem cells are reintroduced by injection. Eventually they grow and repopulate the body with immune cells. The hope is that the new immune cells will no longer attack myelin or other brain tissue, so that the person has perhaps a completely new immune system.
It is not yet clear how much potential benefit may have been due to the transplanted stem cells and how much may have been due to the medications used in the conditioning regimen, as those medications have themselves been preliminarily reported in other studies to be of therapeutic benefit in MS.
This procedure is strictly investigational, and it carries the risk of death because the body is nearly helpless against infection during the several weeks it takes for the immune system to be restored. There is no proof yet that it can cure a person with MS.
Supported, in part, by the National Multiple Sclerosis Society, researchers at the University of Massachusetts in Amherst in the Department of Kinesiology are investigating:
1. The potential source of balance problems and muscle weakness that affect people with all subtypes of multiple sclerosis. There are several studies underway to address each of these aspects of movement and how they may effect everyday activities.
To learn more about this research, or if you are interested in participating, contact Jordan, Jebb, or Stephanie at the Motor Control Laboratory: 413-545-332 or firstname.lastname@example.org http://umass.edu/motorcontrol
2. The causes of muscle weakness in people with multiple sclerosis. The main goal is to understand the causes of muscle weakness in persons with MS, from changes in the nervous system, to the effects of spasticity, to muscle size differences. Knowing the key components to muscle weakness will enable better designs of therapeutic in interventions for improving muscle strength and overall physical function.
To learn more about this research, or if you are interested in participating, contact Linda Chung in the Muscle Physiology Laboratory at 413-545-5305 or email@example.com http://people.umass.edu/muscle
Please note: To participate, you may have to reside near the facility, as treatment and follow-up visits will be necessary throughout the course of the study. Also, please keep in mind that clinical trials often have strict criteria for enrollment, specifying the type of people (disease type, duration, age, etc.) they are seeking to participate. These help to ensure that the results will be as reliable and as effective as possible. If you are interested in participating in a clinical trial we encourage you to discuss the possibility with your personal physicians. Additional studies are listed at the chapter website or our national website.
Study Purpose: Randomized, double-blinded, parallel-group study to assess the efficacy, safety and tolerability of laquinimod compared with placebo or interferon beta-1a (Avonex®).
Type of MS: RR
Questions and Enrollment Information:
- Site: Ayres and Associates Clinical Trials / Upper Valley Neurology. Lebanon, NH
Contact: Terry Kneeland 603.448.3177
Agent: Interferon (IFN) B-1a weekly and glatiramer acetate (GA) daily
Study Purpose: Double-blinded, randomized trial comparing interferon (IFN) B-1a weekly and glatiramer acetate (GA) daily alone or in combination. To affect immune function.
Type of MS: RR
Questions and Enrollment Information:
- Site: Tufts-New England Medical Center, MA
Contact: Amanda Dow 617.636.7671
- Site: Dartmouth Medical School, NH
Contact: Mary Ann Conrad 603.653.9947
Agent: Ocrelizumab (humanized monoclonal antibody)
Study purpose: A randomized, parallel-group, partially blinded, study to evaluate the effectiveness of and safety of 2 dose regimens of ocrelizumab, in comparison with Avonex® and placebo.
Type of MS: RR
Questions and enrollment information:
- Site : Dartmouth Hitchock Medical Center, Lebanon, NH
Contact: Kathleen Ryan 603.653.9919
Agents: AVP-923 (Zenvia)
Study Purpose: A double-blind, randomized, placebo-controlled study to assess the safety and effectiveness and to determine the pharmacokinetics of two doses of AVP-923 for the treatment of pseudobulbar affect (uncontrollable laughing and/or crying) in people with ALS and MS.
Type of MS: All types, with pseudobulbar affect
Questions and Enrollment Information:
- Site: Baystate Medical Center, Springfield, MA
Contact: Elaine Reich 413.794.5856
- Site: Mass General Hospital, Boston MA
Contact: Darlene Pulley 617.726.6190