Excitement About ALS
By Robert G. Miller M.D., director, Forbes Norris MDA/ALS Research and Treatment Center
Amyotrophic lateral sclerosis (ALS) wipes out muscles, paralyzes victims, and leads to death in two to five years. Now for the first time hope is on the horizon.
ALS Clinical Research
The past few years have been incredibly fruitful in fighting the battle against ALS. In the past year alone, there have been five positive ALS clinical trials, an unprecedented series of positive ALS studies. Emerging evidence suggests that neuroinflammation is an important mechanism driving neurodegeneration in ALS (1).
A new drug, NP001, a small molecule that blocks activation of monocytes and macrophages, designed to target neuroinflammation, produced beneficial changes in biomarkers of inflammation with only a single dose2. This is also the first time that a biomarker for ALS has shown a beneficial response in a clinical trial (2).
Another medicine, Dexpramipexole, appeared to slow the disease progress, especially at higher doses, which seem to be very safe (3). Another new compound, CK357, developed in the San Francisco Bay Area, targets the contractile mechanism of skeletal muscle. The drug makes muscles stronger—and early tests in persons with ALS appeared to increase strength and reduce fatigue (4).
A novel approach to treating respiratory insufficiency involves laparoscopic pacemaker insertion into the diaphragm muscle. This procedure has now been carried out in 84 ALS patients, and data suggest a slowing of the decline in breathing function and lengthened survival with excellent safety. The device was just approved by the FDA on the basis of safety and probable benefit (5).
The last advance is a combination of dextromethorphan and low-dose quinidine that is treatment for the excessive emotional outbursts (pseudobulbar affect) that occur in many persons with ALS. This drug was recently FDA approved and appears to be highly effective for this debilitating symptom (6).
New ALS Treatments
There are a number of new treatments for easing the burden of ALS, reviewed in a recent publication of evidence-based management for the disease (7). One drug, Riluzole, slows the progress of the disease and has no major safety concerns. Multidisciplinary specialized clinics, like the Forbes Norris ALS Clinic, provide comprehensive rehabilitation care and treatment plans for persons with ALS. Recent evidence shows that receiving care in a dedicated ALS clinic leads to a higher quality of life, longer life, and greater access to treatments (8).
Noninvasive breathing assistive devices (BiPAP) lengthen life and improve quality of life for those with respiratory insufficiency. When there is swallowing difficulty, nutritional supplements and a feeding tube lengthen survival for ALS patients experiencing severe weight loss. Finally, some patients develop trouble with thinking, and personality changes, as well as difficulty communicating, that require evaluation and treatment.
The progress on the research front is encouraging. Plans are currently under way for the first ALS stem cell trials in California at the Forbes Norris Center and Cedars Sinai in Los Angeles, as well as Emory University in Atlanta, Georgia. While we wait for the cure, advances in symptom management are making a difference for patients and their families. ALS is still incurable; many treatments are available to ensure a longer, more fulfilling life. Unfortunately, outcomes research studies show that these treatments are underutilized. But the trend toward wider use is becoming more evident (9).
- Appel SH, Engelhardt JI, Henkel JS, Siklos L, Beers DR, Yen AA, Simpson EP, Luo Y, Carrum G, Heslop HE, Brenner MK, Popat U. Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology 2008 Oct 21; 71(17):1326-34.
- Miller RG, Katz JS, Forshew DA, Barohn RJ, Kasarskis E, Azhir A, Block G, Zhang R, McGrath MS. Effects of NP001 treatment on monocyte/macrophage activation in patients with ALS. Amyotroph Lateral Sclerosis 2011; 12 (1):49. Abstract.
- Cudkowica M, Bozik ME, Ingersoll EW, Miller R, Mitsumoto h. Shefner J, Moore DH, Schoenfeld D, Mather JL, Archibald D, Sullivan M, Amburgey C, Moritz J, Gribkoff VK. The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis. Nat Med 2011 Nov 20;17(12):1652-6. doi: 10.1038/nm.2579.
- Shefner J, Cudkowic M, Maragakis N. et al; NEALS Group. A Phase 2, Single Dose Study of CK-2017357, a Skeletal Muscle Troponin Activator in Patients with ALS. Neurology 2011; 76 (4):A666. Abstract.
- Onders R, Katirji B, Elmo M, Kaplan C, Schilz R. Current and practical utilization of diaphragm pacing in ALS/MND: From pilot trial experience to FDA humanitarian device approval indications for helping respiration. Amyotroph Lateral Sclerosis 2011; 12 (1):54-55. Abstract.
- Pioro EP, Brooks BR, Cummings J, Schiffer R, Thisted RA, Wynn D, Hepner A, Kaye R. Safety, Tolerability, and Efficacy Results Trial of AVP-923 in PBA Investigators. Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect. Ann Neurol 2010 Nov;68(5):693-702.
- Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: The care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13;73(15):1218-26. Review. Erratum in: Neurology. 2009 Dec 15;73(24):2134. Neurology. 2010 Mar 2;74(9):781.
- The EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis:, Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, Hardiman O, Kollewe K, Morrison KE, Petri S, Pradat PF, Silani V, Tomik B, Wasner M, Weber M. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis (MALS) – revised report of an EFNS task force. Eur J Neurol. 2011 Sep 14. doi: 10.1111/j.1468-1331.2011.03501.x. [Epub ahead of print]
- Miller RG, Anderson F, Brooks BR, Mitsumoto H, Bradley WG, Ringel SP. ALS CARE Study Group. Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database. Ann Neurol. 2009 Jan;65 (1):S24-8.
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