Although electronic communications allow rapid transmission of information among laboratories around the world, face-to-face meetings still play an important role in research. Many new collaborations, contracts, grants and ideas have begun during a coffee break or over dinner when researchers get together.
More than 850 ALS researchers, clinicians and representatives of ALS groups from around the world gathered in Berlin Dec. 8-10, 2009, for the 20th International Symposium on Amyotrophic Lateral Sclerosis/Motor Neuron Disease, organized by the Motor Neurone Disease Association, based in England, Wales and Northern Ireland.
Below are a few highlights from the many reports given at the symposium. Symposium summaries are available online at the Web sites of the Motor Neurone Disease Association and the MDA-supported ALS Therapy Development Institute.
ALSTDI 00846 hits inflammation-related biological targets
Steve Perrin, chief scientific officer at the ALS TDI, presented encouraging results for the experimental drug ALSTDI 00846, being developed by the Institute with funding from MDA.
According to Perrin, who reported on results in mice with an ALS-like disease caused by mutated SOD1 genes, the drug changes a number of markers of inflammation, which is believed to contribute to ALS.
|MDA supports the Massachusetts-based ALS Therapy Development Institute through its Augie’s Quest initiative.
The drug improved survival when administered before symptom onset, but not after, which may sound a bit discouraging. However, Perrin noted that this SOD1 mouse has far more copies of the mutated SOD1 genes per cell than do humans with the SOD1 form of ALS (who have only one copy), so seeing any positive results in this mouse model of the disease is extremely encouraging.
ALS TDI and MDA are planning to carry out further studies of this potential drug.
KNS760704 shows safety, ‘trends’ toward benefit
The experimental drug KNS760704 was reported to be safe and well tolerated, and there were indications of possible benefit, in 92 people with ALS who took it for nine months.
KNS760704 is being developed by Knopp Neurosciences, a Pittsburgh drug discovery company.
Merit Cudkowicz, an investigator on the study who directs the MDA/ALS Center at Massachusetts General Hospital in Boston, announced results of a phase 2 trial of KNS760704. Although she did not receive MDA support for this trial, Cudkowicz has received and continues to receive MDA funding for other ALS research.
According to Knopp, KNS760704 may protect nerve cells under stress. The experimental drug is a molecular mirror image of pramipexole, a prescription medication approved for the treatment of Parkinson’s disease and restless legs syndrome under the trade names Mirapex and Sifrol. The company says these mirror-image molecules have very different properties.
In part 1 of this study, 102 people with ALS were randomly assigned to receive daily doses of 50, 150 or 300 milligrams of KNS760704 or a placebo for three months. There was a trend toward a slowing in the rate of disease progression, as measured by the ALS Functional Rating Scale, across all treatment groups, with greater benefit correlated with higher dosage levels. (“Trends” are results that suggest an effect but can’t be called “significant,” because they don’t reach mathematical criteria for statistical significance.)
In part 2 of the study, which followed a one-month “washout” period, 92 of the original trial participants were randomly assigned to receive either 50 or 300 milligrams per day of KNS760704 for an additional six months. There was a dose-related trend toward a slowed rate of disease progression, and there also was a trend toward a survival benefit in the 300-milligram group compared to the 50-milligram group.
Cudkowicz said the safety results and the trends toward improved functional and survival outcomes observed in this study provide preliminary evidence supporting the ongoing evaluation of KNS760704 in phase 3 clinical trials.
SB509 modestly improves muscle strength
|Strength testing is part of many ALS treatment trials.
According to another report given at the symposium, the experimental compound SB509 appears safe and well-tolerated and may have a positive effect on function in people with ALS.
SB509 is being developed by Sangamo BioSciences, a Richmond, Calif., biotechnology company, which funded this phase 2 trial.
The compound contains the gene for an activator of a protein called vascular endothelial growth factor A (VEGF A). VEGF A protein increases production of blood vessels and may protect or nourish nerve cells.
In people with ALS, VEGF A levels in the spinal fluid are lower than normal, and receptors (docking sites) for VEGF are increased in blood vessels and in the spinal cord, perhaps because the body attempts to compensate for the lower VEGF protein levels.
Forty-five people with ALS are enrolled in the partially completed phase 2 trial, and the symposium report included data from 22 of them.
All trial participants are being treated with SB509. They’re being compared to a “historical” control group — untreated ALS patients who may have been in a placebo group in other trials but are not enrolled in this trial.
Four months after treatment with SB509, six out of 19 people (32 percent) showed improvement on manual muscle testing scores. These trial participants each received two sets of SB509 injections into the muscles of the neck, arms and legs, three months apart.
In the historical control group, 26 out of 153 (17 percent) showed improvement on manual muscle tests.
Five of the six people treated with SB509 who showed improvement with manual muscle testing also improved on the ALS Functional Rating Scale, which assesses physical abilities, and/or a respiratory measurement called forced vital capacity.
The trial took place at California Pacific Medical Center in San Francisco, the University of Kansas Medical Center in Kansas City, and Johns Hopkins University in Baltimore. All three institutions are sites for MDA/ALS centers, from which study participants were drawn (although MDA did not directly support this study).
Jeffrey Rothstein, who directs the MDA/ALS Center at Johns Hopkins University in Baltimore, said the ability to maintain muscle strength or delay its deterioration could have a significant impact on quality of life for people with ALS.