DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Rh deficiency syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRh deficiency syndrome maps to a 3-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 rh deficiency syndrome 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.
Molecular view
Rh associated glycoprotein (RHAG) — RHAG is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet clrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7UZQ · 2.17 Å · ligand CHOLESTEROL (CLR). Experimental structure, not a prediction.
What the evidence adds up to
No abstract in this set mentions Rh deficiency syndrome. The abstracts cover recombinant human growth hormone (rhGH) therapy in children with pseudohypoparathyroidism type Ia, pegylated long-acting rhGH in healthy volunteers, long-acting rhGH preparations in children with growth hormone deficiency, health-related quality of life after childhood rhGH treatment, consequences of adult growth hormone deficiency, and a minimum data set for monitoring rhGH therapy. None of these studies involve patients with Rh deficiency syndrome, and no data on that condition appear in the provided texts.
In the pseudohypoparathyroidism type Ia study, eight prepubertal children received rhGH for 3 to 8 years. Height standard deviation scores improved from -2.4 to -1.8 after 12 months and to -1.15 after three years. Height velocity rose from 3.5 to 7.0 cm per year after three years. However, six patients treated for 4 to 8 years had a reduced pubertal spurt and did not improve near-adult height, except one whose estrogen production was blocked by GnRH analogs. The authors concluded the time window for effective therapy is limited.
The long-acting rhGH studies show that pegylated rhGH produced a dose-dependent increase in IGF-I and IGF binding protein-3 lasting more than a week in healthy volunteers. A 2022 review states that long-acting formulations have shown comparable or higher efficacy than daily rhGH in phase 3 studies, with mild injection-site reactions. The review also notes unresolved concerns about non-physiological GH profiles, long-term metabolic and cancer risk, immunogenicity, and cost-effectiveness. A 2015 study of 300 young adults treated with rhGH in childhood found that health-related quality of life depended on the underlying diagnosis, not on final height. Patients with isolated growth hormone deficiency or idiopathic short stature had physical component scores similar to controls (53.8 vs 54.9), while former cancer patients scored lowest (42.6).
What is still missing for Rh deficiency syndrome specifically: any clinical trial testing rhGH in that population, any pharmacokinetic or pharmacodynamic data in those patients, any long-term safety or efficacy data, and any quality-of-life assessment. The existing rhGH literature cannot be extrapolated to Rh deficiency syndrome without direct evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Clinical Endocrinology & Metabolism · 2010 · 60 citations · open access
Recombinant Human GH Replacement Therapy in Children with Pseudohypoparathyroidism Type Ia: First Study on the Effect on Growth
AbstractCONTEXT: Since the identification of GH deficiency due to resistance to GHRH in patients with pseudohypoparathyroidism type Ia (PHP-Ia), no study investigated the effects of recombinant human GH (rhGH) therapy on height velocity (HV) in these patients. OBJECTIVES, PATIENTS AND METHODS: To address this question, eight prepubertal PHP-Ia children with GH deficiency (seven girls and one boy, aged 5.8-12 yr) underwent a 3- to 8-yr treatment with rhGH. Height and HV were measured before and at 6-month intervals during therapy. Nine sex- and age-matched children with idiopathic GH deficiency were monitored during rhGH therapy for comparison. RESULTS: In PHP-Ia children, height sd scores increased from -2.4 ± 0.58 to -1.8 ± 0.47 (P = 0.04) after 12 months, this increase being maintained after the second (-1.6 ± 0.6) and third (-1.15 ± 0.6) year of therapy, similarly to what recorded in children with idiopathic GH deficiency. The HV and HV sd scores after 3 yr maintained a significant increase from 3.5 ± 0.6 to 7.0 ± 0.9 cm/yr (P < 0.0001) and from -2.8 ± 0.8 to +2.2 ± 1.0 (P < 0.0001), respectively. Six patients treated for 4-8 yr had a reduced pubertal spurt and did not improve their near-adult height, with the only exception of one patient in whom estrogen production was blocked by GnRH analogs. CONCLUSIONS: We report the first study on the efficacy of rhGH replacement therapy in prepubertal children with PHP-Ia and provide indication that treatment of GH deficiency should be started soon due to the rather limited time window for a potentially effective therapy.
The Journal of Clinical Endocrinology & Metabolism · 2010 · 41 citations · open access
Pegylated Long-Acting Human Growth Hormone Is Well-Tolerated in Healthy Subjects and Possesses a Potential Once-Weekly Pharmacokinetic and Pharmacodynamic Treatment Profile
AbstractBACKGROUND: Recombinant human GH (rhGH) is usually administered as a daily sc injection, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed with the aim of reducing serum clearance and thereby prolonging the exposure leading to once-weekly sc administration. OBJECTIVES: In this first human dose trial, the safety, tolerability, pharmacokinetics, and pharmacodynamic parameters of a single administration of NNC126-0083 were evaluated. SUBJECTS AND METHODS: Seven groups of eight healthy male volunteers were dosed once with a single sc administration of NNC126-0083 (n = 6) or placebo (n = 2). The doses were escalated between the cohorts in a sequential mode. Blood samples for assessment of safety, pharmacokinetics, and pharmacodynamic response (IGF-I, IGF binding protein-3, free IGF-I) as well as GH binding protein were taken up to 240 h after dosing. RESULTS: Seven doses of NNC126-0083 were administered. After NNC126-0083 administration, a significant deviation from pharmacokinetic dose proportionality was observed for the highest doses. A strong dose-dependent pharmacodynamic response was seen with elevated levels of IGF-I and IGF binding protein-3 for all doses administered. The elevation was maintained for more than 1 wk for the highest doses. All doses of NNC126-0083 were well tolerated. No local tolerability issues were identified. CONCLUSION: After a single sc administration of NNC126-0083 in healthy male volunteers, a sustained dose-dependent pharmacodynamic response was induced. These results indicate that NNC126-0083 has the potential for an efficacious, well-tolerated, once-weekly rhGH compound in the treatment of GH deficiency in adults.
Hormone Research in Paediatrics · 2022 · 33 citations · open access
Long-Acting Growth Hormone Preparations and Their Use in Children with Growth Hormone Deficiency
AbstractBACKGROUND: Daily recombinant human growth hormone (rhGH) is approved and marketed worldwide to treat children and adults with GH deficiency and other conditions. Efficacy of rhGH therapy is influenced by several variables. Drop of treatment adherence over time has been recognized as a cause of reduced rhGH efficacy and has driven considerable efforts from pharmaceutical companies and scientists to develop long-acting rhGH (LAGH) formulations in order to relieve patients and their families from the burden of daily injections. SUMMARY: Different technologies to manipulate drug release have been produced allowing weekly, biweekly, or monthly rhGH administration. The LAGH formulations developed at present have demonstrated a comparable or even higher efficacy as compared with daily rhGH in most of the cases and no major safety issues in phase 3 studies. A greater incidence of injection-site reactions has been reported but mainly of mild and transient nature. KEY MESSAGES: Despite LAGH analogs appearing promising, potential drawbacks still need to be addressed. Long-term consequences of nonphysiological GH profile and its consequences on metabolism and risk of cancer, optimal therapeutic monitoring, immunogenicity of LAGH molecules, and potential novel side effects related to the technologies used to develop these molecules are among the major concerns that require answers from long-term surveillance. Finally, increased acceptance of LAGH formulations from patients and their caregivers is yet to be demonstrated and cost-effectiveness evaluated consequently.
Health-Related Quality of Life of Young Adults Treated with Recombinant Human Growth Hormone during Childhood
AbstractBACKGROUND: Since recombinant human growth hormone (rhGH) became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL) after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood. METHODOLOGY/PRINCIPAL FINDINGS: For this study, we retrospectively identified former rhGH patients in 11 centers of paediatric endocrinology, including university hospitals and private practices. We sent a questionnaire to all patients treated with rhGH for any diagnosis, who were older than 18 years, and who resided in Switzerland at time of the survey. Three hundred participants (58% of 514 eligible) returned the questionnaire. Mean age was 23 years; 56% were women; 43% had isolated growth hormone deficiency, or idiopathic short stature; 43% had associated diseases or syndromes, and 14% had growth hormone deficiency after childhood cancer. Swiss siblings of childhood cancer survivors and the German norm population served as comparison groups. HRQoL was assessed using the Short Form-36. We found that the Physical Component Summary of healthy patients with isolated growth hormone deficiency or idiopathic short stature resembled that of the control group (53.8 vs. 54.9). Patients with associated diseases or syndromes scored slightly lower (52.5), and former cancer patients scored lowest (42.6). The Mental Component Summary was similar for all groups. Lower Physical Component Summary was associated with lower educational level (coeff. -1.9). Final height was not associated with HRQoL. CONCLUSIONS/SIGNIFICANCE: In conclusion, HRQoL after treatment with rhGH in childhood depended mainly on the underlying indication for rhGH treatment. Patients with isolated growth hormone deficiency/idiopathic short stature or patients with associated diseases or syndromes had HRQoL comparable to peers. Patients with growth hormone deficiency after childhood cancer were at high risk for lower HRQoL. This reflects the general impaired health of this vulnerable group, which needs long-term follow-up.
Wiedza Medyczna · 2023 · 0 citations · open access
The consequences of growth hormone deficiency in adults
AbstractAdult growth hormone deficiency (GHD) is a result of the decreased growth hormone (GH) production and secretion from the anterior pituitary gland in adulthood, that cannot be explained by the physiological ageing process. GHD is associated with numerous deleterious consequences such as adverse changes in body composition, carbohydrate and lipid metabolism, alterations in the cardiovascular system, and deterioration in the quality of life (QoL). Most of these complications are at least partially reversible during recombinant human growth hormone (rhGH) replacement therapy. Thus, physicians and particularly endocrinologists, should consider GHD diagnosis and select patients who could benefit from rhGH therapy.
Journal of the Endocrine Society · 2023 · 0 citations · open access
THU166 A Minimum Data Set For The Monitoring Of Recombinant Human Growth Hormone (rhGH) Therapy In Children With Growth Hormone Deficiency (GHD)—A GloBE-Reg Initiative
AbstractAbstract Disclosure: S.C. Chen: None. E. Charmandari: None. J. Choi: None. X. Dou: None. C. Gong: None. R. Hamza: None. J. Harvey: None. A.R. Hoffman: None. R. Horikawa: None. G. Johannsson: None. A.A. Jorge: None. B.S. Miller: None. S. Roehrich: None. L.S. Savendahl: None. X. Tserotopolou: None. M.P. Wajnrajch: None. S.F. Ahmed: Grant Recipient; Self; Novo Nordisk. Objective Although there are some recommendations in the literature on the assessments that should be performed in children on rhGH therapy, the level of consensus on these measurements and their frequency for routine clinical practice is unclear. The objective of this study was to identify a minimum dataset (MDS) to be captured in routine clinical settings for children receiving all forms of rhGH therapy for GH deficiency (GHD). Methods This exercise was undertaken through the collaborative efforts of a group of experts who form the GH Scientific Study Group (SSG) in GloBE-Reg, a new international registry platform developed in close collaboration with clinicians, patients and industry and which can support long-term safety and effectiveness studies for drugs that require such surveillance. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, two patient advocates and representatives from two industry partners with previous GH registry expertise developed a comprehensive list of data fields routinely collected for children with GHD. Members graded the: (1) Importance of the field and (2) Ease of data collection. Fields that achieved a minimum of 70% consensus for importance qualified for the MDS, provided &lt;50% deemed the item difficult to collect. Results Of 225 items graded, 113 (50%) items achieved at least 70% consensus as important to collect. Of the 225 items, 69 (31%) were deemed easy to collect and combining the criteria of importance and ease of data collection, 64 (28%) met both criteria for the MDS. Some other items including patient involvement in clinical trials, HbA1c in long-acting rhGH therapy and adherence did not meet the MDS criteria but were considered to be important enough to be included and some of the items were merged into one item. The final MDS consisted of 43 items; 20 to be entered once, 14 every 6 months and 9 every 12 months. Conclusions In summary, this exercise formulated the minimum dataset for the GloBE-Reg GH module which was launched in October 2022 for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and also the newer long-acting growth hormone. Additional modules are being developed for specific GH products and other therapies for growth disorders. More information about the study and instructions on how to participate are available on the project’s website: www.globe-reg.net. Presentation: Thursday, June 15, 2023
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.
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