Prolactin Is THE Root Cause of Hair Loss?! Absci’s New Drug May Prove It

Scientific Concepts / Discoveries / Nature Phenomena

Central hypothesis: prolactin as a driver of androgenetic alopecia (AGA)

• Traditional view: DHT (androgens) is the primary causal hormone in pattern hair loss / androgenetic alopecia.
• Newer “root-cause” hypothesis: prolactin may be upstream of androgen signaling and hair follicle miniaturization (proposed by multiple researchers and advanced by ABSI).

Proposed mechanisms

• Prolactin increases androgen receptor (AR) expression, potentially amplifying downstream DHT effects on hair follicles.
• Prolactin may also contribute to stem cell niche degradation in the hair follicle bulge, reducing regenerative capacity.

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Tissue vs blood hormone levels

• Prolactin may be locally elevated in the scalp even when systemic (blood) prolactin is normal.
• A suggested reason for missed connections:
  • Past comparisons may have relied on blood prolactin, without measuring local scalp prolactin expression (including extra-pituitary sources).

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Receptor occupancy / “receptor reserves” (spare receptors)

• ABSI argues earlier prolactin-receptor blockade (e.g., HMI 115) may have undershot effective receptor occupancy in humans.
• Introduced concept:
  • Receptor reserves: cells can maintain full pathway activity despite not fully blocking all receptors.
  • Therefore, partial blockade (e.g., ~80%) might still leave signaling “good enough” for the pathway to function.
• ABSI claim:
  • Their newer drug aims for sustained >90% prolactin receptor occupancy for ~6 months, intending to surpass the spare-receptor threshold so hair stem-cell niche recovery can occur.

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Hair follicle biology mechanisms discussed

AGA may involve “rate-limiting” barriers that DHT-targeting and growth-stimulating therapies may not fully address:

1. Fibrosis / scarring (parafollicular fibrosis) preventing normal regeneration
2. Detachment from the erector pilli muscle after miniaturization
3. Stem cell failure: hair follicle stem cells lose the ability to produce progenitor cells, limiting regeneration

ABSI’s mechanistic target

Blocking prolactin signaling is proposed to:

• Increase K15+ stem cell proliferation
• Prevent apoptosis of those stem cells
• Preserve CD34+ progenitor populations
• Modulate collagen 17A, described as anchoring the stem cell niche to the follicle

These changes are framed as enabling true regeneration, not merely improved cycling.

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Preclinical evidence pathway described (mice → stumptailed macaques → humans)

1) Mouse study (via Bear / HMI 115)

• A prolactin pathway-lowering drug (HMI 115) produced faster hair regrowth vs placebo in mice.
• Caveat noted: translation limitations, since mice do not naturally develop male-pattern baldness.

2) Stumptailed macaque study (via Bear)

• Monkeys were treated in the context of prolactin receptor antibodies (HMI 115 background).
• Reported outcomes:
  • After ~6 months: large hair regrowth
  • After stopping treatment: regrowth continued for ~4 more years
  • Reported pigmentation effect: gray hair repigmented back toward colored hair
• Claimed significance: magnitude of regrowth and repigmentation was presented as unusual vs typical AGA recovery patterns.

3) Early human trials (phase 1/2 for HMI 115)

• Phase 1 press release:
  • Small sample size (16 people)
  • Reported safety
  • Limited hair regrowth (e.g., ~14 hairs/cm² stated)
• Phase 2:
  • Described as completed, but results reportedly not submitted/published by the company (per the narrator’s account).
• Interpretation offered:
  • Andreas Bush (linked to earlier work) suggests failure may reflect dose / receptor occupancy, not that prolactin is irrelevant.

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Drug evolution and targets

• HMI 115 (Bear; prolactin pathway/receptor blockade):
  • Claimed underperformance in humans.
• ABS 2011 / ABSI’s prolactin receptor antibody:
  • Designed to address suspected limitations of earlier blockade (insufficient receptor occupancy and insufficient duration above an effective threshold).
  • Claimed goal: enable regenerative restoration by preserving stem cell niche function.

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Clinical trial status mentioned

• ABSI’s drug is in Phase 2 clinical trials for androgenetic alopecia.
• Planned reporting timeline:
  • 13-week readout expected in December
  • “Directional” efficacy goals described, with a pathway toward 30+ hairs/cm² at ~26 weeks
• Follow-up:
  • Participants followed for about 1 year post-treatment to assess durability and progression.

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Data integrity / reporting expectations (as discussed)

• The narrator argues hair-loss industry reporting has sometimes used misleading statistical methods.
• ABSI founder (per the video narrative) promises a “non-controversial” data cut and avoiding “subpopulation-of-subpopulation” style analyses.

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Methodologies / Experimental Logic Outlined

• Therapeutic hypothesis testing

  • Block prolactin signaling using prolactin receptor antibodies
  • Compare hair outcomes to placebo / untreated controls

• Animal translation strategy

  • Start in mice to test proof-of-concept regrowth direction
  • Move to a species that can naturally go bald: stumptailed macaques
  • Evaluate long-term outcomes after treatment withdrawal

• Human mechanistic exploration via ex vivo scalp culture

  • Obtain human scalp biopsies from AGA areas
  • Culture under conditions:
    • Untreated control
    • ABS 2011 alone
    • Prolactin alone
    • Prolactin + ABS 2011 (rescue condition)
  • Measure hair-cycle-related growth changes over short periods (e.g., described 3-day culture readouts)

• Mechanism focus: stem cell niche preservation

  • Assess markers such as:
    • K15+ stem cell proliferation
    • apoptosis changes
    • CD34+ progenitor levels
    • collagen 17A niche anchoring

• Dose rationale via pharmacokinetics

  • Use publicly disclosed PK data to estimate:
    • receptor occupancy (RO)
    • time above an inferred effective threshold
  • Target goal described: sustained >90% RO

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Researchers / Sources Featured (as Named in Subtitles)

• Rob English — video host; hair loss researcher and scientific reviewer
• Shawn Mlan — ABSI founder; central interviewee
• Andreas Bush — researcher at Bear; linked to HMI 115 and the monkey/human rationale
• Bear Pharmaceuticals — company referenced for the HMI 115 research program
• Hope Medicine — mentioned as licensing/partnering for human studies
• ABSI — company developing ABS 2011 / anti-prolactin receptor antibody
• Ralph Paws — 2006 paper; reported prolactin production and shedding effects in human follicle biopsies
• UK Biobank — genetic data source used for prolactin receptor-expression vs hair-loss severity analysis
• Vertex — mentioned as prior employer of ABSI’s chief medical officer
• Amgen — mentioned as another prior employer of ABSI’s chief medical officer
• Verodermics — mentioned during adverse-event reporting discussion (named source)