DeCure for Congenital muscular dystrophy due to integrin alpha-7 deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital muscular dystrophy due to integrin alpha-7 deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital muscular dystrophy due to integrin alpha-7 deficiency maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for congenital muscular dystrophy due to integrin alpha-7 deficiency is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
A single case report describes a Chinese boy from a consanguineous family who carries a homozygous variant (c.1088dupG, p.H364Sfs*15) of the ITGA7 gene, identified by whole exome and targeted sequencing of four family members. The boy was diagnosed with congenital muscular dystrophy (CMD), a group of early-onset disorders characterised by muscle weakness from birth or early infancy, delayed or arrested gross motor development, and joint or spinal rigidity. The report confirms autosomal recessive inheritance for this ITGA7 mutation and adds to the known genetic heterogeneity of CMD. No treatment, drug, or intervention was tested or proposed in this study.
The paper does not provide any data on survival, response rates, or sample sizes beyond the single patient. It states that identification of disease-causing genes facilitates diagnosis and treatment, but offers no evidence of any therapeutic effect. The conclusions emphasise the role of genetic counselling and multidisciplinary management, and note that further elucidation of clinical and genetic heterogeneity, therapeutic targets, and clinical care remains a challenge.
No drug is mentioned in any of the provided abstracts. There is no information on repurposing, preclinical models, or any pharmacological intervention for integrin alpha-7 deficiency. The report is purely diagnostic and genetic in nature.
What is still missing is any clinical trial, any tested therapy, any patient stratification beyond a single family, and any funding directed toward treatment development for this specific CMD subtype. Without such studies, no evidence exists to support any drug for this condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Genetics · 2021 · 10 citations · open access
Case Report: A Boy From a Consanguineous Family Diagnosed With Congenital Muscular Dystrophy Caused by Integrin Alpha 7 (ITGA7) Mutation
AbstractIntroduction: Congenital muscular dystrophy (CMD) is a group of early-onset disorders with clinical and genetic heterogeneity. Patients always present with muscle weakness typically from birth to early infancy, delay or arrest of gross motor development, and joint and/or spinal rigidity. There are various genes related to the development of CMD. Among them, mutations in integrin alpha 7 ( ITGA7 ) is a rare subtype. The identification of disease-causing genes facilitates the diagnosis and treatment of CMD. Methods: We screened ITGA7 mutations in four people by whole exome sequencing and targeted sequencing from a consanguineous family. We then carried out electromyography and neuroelectrophysiological examinations to clarify a clinical picture of the patient diagnosed with CMD. Results: We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs * 15) of the ITGA7 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. Conclusions: Our case further shows that ITGA7 mutation is related to CMD. Genetic counseling and multidisciplinary management of CMD play an important role in helping patients and their family. Further elucidation of the significant clinical and genetic heterogeneity, therapeutic targets, and the clinical care for patients remains our challenge for the future.
Developmental Medicine & Child Neurology · 2009 · 8 citations · open access
‘Congenital muscular dystrophy caused by integrin α7 deficiency’
AbstractSIR–Hayashi et al. reported three male children with integrin α7 deficiency.1 The first patient in this series had splice mutations on both alleles of the integrin α7 gene, rolled over at 9 months, walked at 2 years 6 months, and could not jump or run. Learning disability* was also observed, and the patient could speak only a few words. The second patient, a compound heterozygote for the same base deletion, acquired independent ambulation at 2 years 1 month and could not run. The third patient showed marked reduction of integrin α7 mRNA. He was born by Cesarean section because of breech presentation. His gestational age was 39 weeks, and his birth weight was 3024g. He had no family history of muscular disease. Hypotonia was seen from birth. The head was steady at 8 months, he sat without support at 1 year 2 months, and he moved on his knees at 2 years 8 months. His motor development then stopped and started regressing at age 5 years. Muscle weakness and atrophy, predominantly of the proximal muscles, progressed. No abnormalities were found on magnetic resonance imaging of the head. On histology, the muscles from these three patients showed little or no evidence of myofiber necrosis and regeneration. There have been no reports of the long-term clinical course of this disease. In order to determine the prognosis of this disease, we describe the clinical course of the third patient. The patient could only move by bottom shuffling at 7 years of age and he showed gradually progressive dyspnea at 8 years 10 months. He was admitted to Seirei Mikatahara General Hospital, Shizuoka, Japan, at 8 years 11 months after developing marked dyspnea. His vital signs were: temperature, 36.5°C; heart rate, 128 beats/min; respiratory rate, 28 breaths/min. Normal vesicular breath sounds were heard in both lungs, the heart sounds were normal, and no murmurs were heard. Laboratory data showed: white blood cell count, 10,900/μl; red blood cell count, 441 × 104/μl; hemoglobin, 12.3 g/dl; hematocrit, 40.7%; platelets, 31.3 × 104/μl; aspartate aminotransferase, 31 IU/L; alanine aminotransferase, 17 IU/L; lactate dehydrogenase, 258 IU/L; creatine kinase, 259 IU/L; creatinine, 0.1 mg/dl; blood urea nitrogen, 10 mg/dl; sodium, 140 mEq/L; potassium, 4.3 mEq/L; chloride, 99 mEq/L; and human atrial natriuretic peptide, 44 pg/ml. Blood gas analysis revealed: pH 7.266; PaCO2 79.4 mmHg; PaO2 62.4 mmHg; HCO3 36.1 mEq/L; base excess 7 mEq/L; and SpO2 87.3%. No infiltration was apparent on chest X-ray and marked scoliosis prevented us from measuring the cardiothoracic ratio. The Cobb angle was 73°. On cardiac ultrasound, the left ventricular end-diastolic dimension was 30.5 mm, the end-systolic dimension was 19.7 mm, and fractional shortening was 35.6%. We concluded that the dyspnea was caused by respiratory muscle weakness, since his cardiac function was normal. Non-invasive positive pressure ventilation was started, and his dyspnea improved. The patient was discharged from hospital 8 days later. The patient became wheelchair-bound at 12 years of age. His scoliosis was progressive, and his mental development was normal throughout life. His intelligence quotient (IQ) as evaluated using the Wechsler Preschool and Primary Scales of Intelligence2 at 6 years and 1 month showed: Verbal IQ 86; Performance IQ 123; and Total IQ 104. The basal lamina of the muscle fibers is important in the development and function of skeletal muscle, and integrin α7β1D is a muscle-specific laminin receptor.3,4 In a previous report, integrin α7 deficiency was categorized as ‘congenital myopathy’ because this disorder is thought to result from abnormal muscle development.1 We found that very severe cases of integrin α7 deficiency exist. The severity of this manifestation in the present case was almost equal to that of Duchenne muscular dystrophy; though hypotonia was seen soon after birth, cardiac function has remained unimpaired, and the patient’s intelligence is normal. We must keep integrin α7 deficiency in mind when we encounter patients with unclassified congenital muscular dystrophy or congenital myopathy. More cases must be collected, and further studies are needed.
Table_1_Case Report: A Boy From a Consanguineous Family Diagnosed With Congenital Muscular Dystrophy Caused by Integrin Alpha 7 (ITGA7) Mutation.docx
Abstract<p>Introduction: Congenital muscular dystrophy (CMD) is a group of early-onset disorders with clinical and genetic heterogeneity. Patients always present with muscle weakness typically from birth to early infancy, delay or arrest of gross motor development, and joint and/or spinal rigidity. There are various genes related to the development of CMD. Among them, mutations in integrin alpha 7 (ITGA7) is a rare subtype. The identification of disease-causing genes facilitates the diagnosis and treatment of CMD.</p><p>Methods: We screened ITGA7 mutations in four people by whole exome sequencing and targeted sequencing from a consanguineous family. We then carried out electromyography and neuroelectrophysiological examinations to clarify a clinical picture of the patient diagnosed with CMD.</p><p>Results: We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs<sup>*</sup>15) of the ITGA7 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance.</p><p>Conclusions: Our case further shows that ITGA7 mutation is related to CMD. Genetic counseling and multidisciplinary management of CMD play an important role in helping patients and their family. Further elucidation of the significant clinical and genetic heterogeneity, therapeutic targets, and the clinical care for patients remains our challenge for the future.</p>
Image_1_Case Report: A Boy From a Consanguineous Family Diagnosed With Congenital Muscular Dystrophy Caused by Integrin Alpha 7 (ITGA7) Mutation.jpg
Abstract<p>Introduction: Congenital muscular dystrophy (CMD) is a group of early-onset disorders with clinical and genetic heterogeneity. Patients always present with muscle weakness typically from birth to early infancy, delay or arrest of gross motor development, and joint and/or spinal rigidity. There are various genes related to the development of CMD. Among them, mutations in integrin alpha 7 (ITGA7) is a rare subtype. The identification of disease-causing genes facilitates the diagnosis and treatment of CMD.</p><p>Methods: We screened ITGA7 mutations in four people by whole exome sequencing and targeted sequencing from a consanguineous family. We then carried out electromyography and neuroelectrophysiological examinations to clarify a clinical picture of the patient diagnosed with CMD.</p><p>Results: We report a Chinese boy diagnosed with CMD who carries a homozygous variant (c.1088dupG, p.H364Sfs<sup>*</sup>15) of the ITGA7 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance.</p><p>Conclusions: Our case further shows that ITGA7 mutation is related to CMD. Genetic counseling and multidisciplinary management of CMD play an important role in helping patients and their family. Further elucidation of the significant clinical and genetic heterogeneity, therapeutic targets, and the clinical care for patients remains our challenge for the future.</p>
Annals of Clinical Neurophysiology · 2018 · 0 citations · open access
Novel recessive mutations of <i>COL6A1</i> identified in the early severe phenotype of ullrich congenital muscular dystrophy
AbstractUllrich congenital muscular dystrophy (UCMD) is caused by mutations in one of three genes encoding collagen VI. Although UCMD usually shows an early onset, progressive weakness, contractures and hyperlaxity of the joints, and respiratory failure, it is well known to exhibit a wide spectrum of clinical severities. The severities of the phenotypic subtypes are mainly divided according to the ambulation status. We report a patient with the early-severe phenotype of UCMD who was diagnosed by the detection of novel recessive mutations in COL6A1.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
