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[[Gene therapy for osteoarthritis]] is also being investigated as technology to create a drug that would act as a disease modifying drug.
[[Gene therapy for osteoarthritis]] is also being investigated as technology to create a drug that would act as a disease modifying drug.

[[Paroxetine]] has been deemed to have dmoad activity.<ref>{{Cite journal|last=Carlson|first=Elijah L.|last2=Karuppagounder|first2=Vengadeshprabhu|last3=Pinamont|first3=William J.|last4=Yoshioka|first4=Natalie K.|last5=Ahmad|first5=Adeel|last6=Schott|first6=Eric M.|last7=Le Bleu|first7=Heather K.|last8=Zuscik|first8=Michael J.|last9=Elbarbary|first9=Reyad A.|last10=Kamal|first10=Fadia|date=2021-02-10|title=Paroxetine-mediated GRK2 inhibition is a disease-modifying treatment for osteoarthritis|url=https://pubmed.ncbi.nlm.nih.gov/33568523/|journal=Science Translational Medicine|volume=13|issue=580|doi=10.1126/scitranslmed.aau8491|issn=1946-6242|pmid=33568523}}</ref>


== References ==
== References ==

Revision as of 20:56, 5 June 2021

A disease-modifying osteoarthritis drug (DMOAD) is a drug that would inhibit or even reverse the progression of osteoarthritis.[1] Since the main hallmark of osteoarthritis is cartilage loss, a typical DMOAD would prevent the loss of cartilage and potentially regenerate it. Other DMOADs may attempt to help repair adjacent tissues by reducing inflammation. A successful DMOAD would be expected to show an improvement in patient pain and function with an improvement of the health of the joint tissues.[2]

Approved for human use

There are currently no DMOADs approved for human use.

Drugs with undergoing human trials

Drug Mechanism of Action Status Investigator(s)
AKL4 / APPA[3] Oral NFkB and Nrf2 modulator National Institute for Health Research (NIHR)-approved Phase I study successfully completed 1Q 2020.

Phase 2 150-patient started 4Q 2020 with NBCD (Nordic Bioscience) and due to complete 3Q 2021.[4]

AKL Research & Development[5]
SM04690 / Lorecivivint[6] Wnt pathway inhibitor Phase 2 study completed, showing improvement in pain, function and joint space width.[7]

Phase 3 study started in May 2019.[8]

In May 2020, it was reported that phase 2a trial failed to meet primary endpoint.[9][10] But a phase 2b trial in early 2021 met primary endpoint.[11]

BioSplice(ex-Samumed) expects to release phase3 results in late 2021.[12]

Samumed
KA34 / Kartogenin Induces MSCs to differentiate into chondrocytes[13] via its lytic product 4-aminobiphenyl (known as a carcinogen)[14] Phase 1 study started in May 2018 to evaluate safety of kartogenin in humans.[15] Calibr[16]
UBX0101 p53/MDM2 inhibitor, induces apoptosis of senescent cells to create a favourable healing environment[17] Phase 1 study complete in June 2019,[18] results were encouraging leading to plans for a phase 2 study. Phase 2 study results did not show any improvements and led to drug being discontinued from investigation.[19] Unity Biotechnology
BMP7 Supports transcription of osteogenic genes[20] Phase 1 study completed in 2010.[21]

Phase 2 study completed in 2015,[22] suggesting the ability to prevent cartilage loss.

Ember Therapeutics[23]
TPX-100 23-amino acid peptide that induces articular cartilage formation [24] reduces pathological shape change of joint bones.[25] A one-year study of 93 patients revealed that TPX-100 treatment was associated with significant and sustained improvements in critical knee functions, preservation of knee cartilage thickness, reduced pathologic changes in underlying bone, and a >60% decrease in use of pain medications.[26][27] Orthotrophix
FGF-18 / Sprifermin Promote chondrogenesis through fibroblast growth factor receptor FGFR3[28] Phase 2 study completed in 2017, with results failing to show improvement in pain or function. It did however show prevention of cartilage loss meaning it may be able to be used as a prevention. Merck

Nordic Biosience

LNA043 Chondrogenesis enhancer[29] Phase 1 study started in 2015.[30] Novartis
GLPG1972 ADAMTS-5 inhibitor Phase 1 study completed in 2019.

Phase 2 study started in 2019.[31]

In October 2020, Servier reported phase 2 trial failed.[32]

Galapagos
M6495 ADAMTS-5 inhibitor Phase 1 safety study completed.[33] Novartis[34]
MIV-711 Cathepsin K inhibitor[35] Phase 2 study completed in 2019, showing prevention of cartilage damage but did not show reduction in patient pain.[36] Medivir
Invossa-K Cell/Gene therapy Human studies halted by FDA for false ingredient claim.[37][38]There are claims fda allowed for phase 3 trials to resume in the US.[39] Kolon Life Science
Amniotic fluid allograft (ReNU, Palingen InovoFlo, AmnioFix, Clarix Flo) Note: Amniotic fluid is not a single drug and instead contains around 226 growth factors,[40] including BMP7.

Inflammation reducer[41] and cartilage growth enhancer.[42]

Initial 6 patient study in 2015 showed improvement in pain and function.[43] A randomised controlled trial of 200 patients completed in 2019,[44] also showing improved pain and function.

A 2019 non-randomised study in 20 patients showed improvement in joint tissue health.[45]

Organogenesis

Amnio Technology

MiMedx

Amniox Medical, Inc.

Polysulfate Sodium (PPS) Pentosan Polysulfate Sodium (PPS) is a semi-synthetic drug manufactured from European beech xylans that are sulfated to produce a negatively charged product that mimics glycosaminoglycans (GAGs). Paradigm is proceeding with the submission of the Investigational New Drug (IND), followed by two phase 3 studies commencing in 2021. The pivotal study will be conducted in the US and include 750 subjects while the confirmatory study of 400 subjects is likely to run in Europe and possibly Australia. The two studies will run concurrently. [46][47][48] Paradigm Biopharma (ASX:PAR)

Drugs under investigation

Drug Mechanism of Action Status Investigator(s)
A2M Protect chondrocytes from damage A2M inhibited catabolic activity in rats.[49]

Note: Cytonics offers autologous A2M therapy in humans but no randomised human trials have been published to date. A human trial is underway at NYU.[50]

Cytonics
SS-31 Mitoprotective peptide Study done on 2 horses[51] showed protective effects in vivo. Cornell
TD-198946 Chondrogenic factor[52] Basic science studies being carried out. University of Tokyo[53]
M6495 ADAMTS-5 inhibitor[54] Shown to protect against cartilage breakdown in cartilage and synovial joint tissue explant models[55] Merck
B001-5 ADAMTS-5 and ADAM-17 inhibitor[56] To be submitted to FDA in early 2020.[56] Guangzhou Institutes of Biomedicine and Health

Gene therapy for osteoarthritis is also being investigated as technology to create a drug that would act as a disease modifying drug.

Paroxetine has been deemed to have dmoad activity.[57]

References

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  2. ^ "New targets in osteoarthritis are about more than just pain". Biocentury Innovations.
  3. ^ "About APPA". AKL Research & Development Ltd. Retrieved 2020-11-24.
  4. ^ Development (AKLRD), AKL Research and. "AKL Research & Development's novel osteoarthritis medicine APPA begins Phase II trial with partner Nordic Bioscience Clinical Development". www.prnewswire.com. Retrieved 2020-11-24.
  5. ^ "Home". AKL Research & Development Ltd. Retrieved 2020-11-24.
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Disease-modifying Osteoarthritis Drug (DMOAD)

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