Boston ’s Flex Pharma slashes headcount, eyes sale after ALS drug fails

Boston-based Flex Pharma will lay off most of its employees and explore a potential sale or merger after ending a mid-stage trial of its lead drug, which targets several diseases including amyotrophic lateral sclerosis, or ALS. Flex (Nasdaq: FLKS) announced Wednesday that it had halted a Phase 2 study of the drug, called FLX-787, in patients with either ALS or neurological disorder Charcot-Marie-Tooth disease. The company cited “oral tolerability concerns,” though it said that the drug had helped…
Source: Health Care:Pharmaceuticals headlines - Category: Pharmaceuticals Authors: Source Type: news

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Authors: Feng SY, Feng SM, Li LY, Zou ZY PMID: 29629536 [PubMed]
Source: Journal of Clinical Neurology - Category: Neurology Tags: J Clin Neurol Source Type: research
AbstractHeterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygousde novo frame-shift mutations in the C-terminal domain ofKIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations inKIF5A are also a ca...
Source: Brain - Category: Neurology Source Type: research
AbstractThe clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms. It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder. The advent of next generation sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all gene variants in the genome simultaneously. With the plethora of new genes being identified, genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia (SCA), hereditary spastic ...
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
The valosin-containing protein (VCP) is involved in a plethora of cellular processes including membrane dynamics, DNA damage response, and protein quality control.1 Its essential role in humans is highlighted by diverse clinical phenotypes linked to VCP mutations: (1) inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD); (2) amyotrophic lateral sclerosis; (3) Charcot-Marie-Tooth disease type 2; and (4) hereditary spastic paraplegia (reviewed by Evangelista et al.2). Moreover, mutant VCP has been implicated in the pathogenesis of Parkinson disease (PD).3
Source: Neurology - Category: Neurology Authors: Tags: All Medical/Systemic disease, Parkinson's disease/Parkinsonism, Peripheral neuropathy, Muscle disease CLINICAL/SCIENTIFIC NOTES Source Type: research
In this study, we examined the non-cell autonomous role of wild type and mutant HSPB1 in an astrocyte-motor neuron co-culture model system of ALS. Astrocyte-specific overexpression of wild type HSPB1 was sufficient to attenuate SOD1(G93A) astrocyte-mediated toxicity in motor neurons, whereas, overexpression of mutHSPB1 failed to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting that phosphorylation may contribute to HSPB1 mediated-neuroprotection. These data provide evidence that astrocytic HSPB1 expression may play a ce...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
Conclusions:Corticospinal tract lesions have a heterogenous etiology, with widely different treatments and prognoses. An understanding of these potential etiologies will assist neurologists confronted with this imaging finding.Study Supported by: None.Disclosure: Dr. Wallach has nothing to disclose. Dr. Stember has nothing to disclose. Dr. Valentine has nothing to disclose. Dr. Howard has nothing to disclose.
Source: Neurology - Category: Neurology Authors: Tags: General Neurology: Practice Improvement and Novel Approaches to Care Source Type: research
Conclusions:Our findings suggest that the mutant LRSAM1 may aberrantly affect the formation of transcription machinery. Given a similar mechanism has been reported in motor neuron degeneration of amyotrophic lateral sclerosis, abnormalities of RNA-binding protein complex may play a role in the neuronal degeneration of CMT2P.Study Supported by:This research is supported by grants from NINDS (R01NS066927 to J.L.; R01NS075764, 5R01NS072248, and U54NS065712 to S.Z.), the MDA and the National Center for Advancing Translational Sciences (UL1TR000445).Disclosure: Dr. Li has nothing to disclose. Dr. Hu has nothing to disclose. Dr....
Source: Neurology - Category: Neurology Authors: Tags: Peripheral Nerve Disorders Source Type: research
This study also identified a de novo c.3015_3027dup frameshift mutation predicting p.Lys1010Glnfs*57 in NEFH from a CMT2 family with an atypical clinical symptom of prominent proximal weakness. This mutation is located near the previously reported frameshift mutations, suggesting a mutational hotspot. Lower limb MRI revealed marked hyperintense signal changes in the thigh muscles compared to those in the calf muscles. Therefore, this study suggests that the stop loss and translational elongations by the 3’ UTR of the NEFH mutations may be a relatively frequent genetic cause of axonal peripheral neuropathy with the sp...
Source: Journal of the Peripheral Nervous System - Category: Neurology Authors: Tags: CASE REPORT Source Type: research
Abstract Mutations in SPG11 account for the most common form of autosomal recessive hereditary spastic paraplegia (HSP), characterized by a gait disorder associated with various brain alterations. Mutations in the same gene are also responsible for rare forms of Charcot-Marie-Tooth (CMT) disease and progressive juvenile-onset amyotrophic lateral sclerosis (ALS). To elucidate the physiopathological mechanisms underlying these human pathologies, we disrupted the Spg11 gene in mice by inserting stop codons in exon 32, mimicking the most frequent mutations found in patients. The Spg11 knockout mouse developed early-on...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Conclusions: The PR of all adult NMD in RoI is relatively high when compared with other chronic neurologic disorders, although some figures may be an underestimate of the true prevalence. The data provide a framework for international comparison and service planning.
Source: Neurology - Category: Neurology Authors: Tags: All Neuromuscular Disease, Myasthenia, Peripheral neuropathy, Muscle disease, Prevalence studies ARTICLE Source Type: research
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