Dr. Austin Fontenot

Blog posts

Emerging Therapies

Understand how experimental treatments are assessed, validated, and responsibly introduced into rehabilitation care.

A photorealistic image of a researcher in a modern but grounded biomedical laboratory. A scientist in a white lab coat sits at a clean workstation examining tissue samples under a high-powered microscope. Nearby: standard lab equipment β€” a centrifuge, pipettes, labeled specimen vials, a notebook with handwritten notes, and a computer monitor showing a research paper or data spreadsheet. The lighting is natural and bright β€” overhead fluorescent lab light with warm daylight coming through a window. The atmosphere is focused and methodical: serious science being done carefully and deliberately. No glowing fluids, no holograms, no robotic arms. Photographic realism, documentary style, clean and professional.

⚠ Medical Disclaimer

This page is for educational purposes only. The therapies discussed below are in various stages of clinical investigation. None of this content constitutes medical advice, a clinical recommendation, or an endorsement of any specific treatment. Consult a licensed healthcare provider before pursuing any emerging therapy.

What Makes a Therapy β€˜Emerging’?

Emerging therapies occupy the space between laboratory promise and clinical standard of care. They carry enough biological plausibility and early human data to attract serious research attention, yet lack the volume of high-quality randomized controlled trials (RCTs) required for guideline-level endorsement. Understanding what qualifies a therapy as β€œemerging” helps patients and clinicians evaluate new treatment options with appropriate optimism and appropriate skepticism.

Three defining features of an emerging therapy:

  • Biological plausibility β€” a credible, proposed mechanism of action supported by basic science or prior clinical analogy.
  • Early human data β€” at least pilot-level or Phase I/II clinical evidence demonstrating initial safety and preliminary efficacy signals.
  • Active investigation β€” ongoing trials registered in ClinicalTrials.gov or actively reported in peer-reviewed literature.

Cite: Sackett DL et al. Evidence-based medicine. BMJ. 1996;312:71. Β |Β  Freedman B. Equipoise and the ethics of clinical research. NEJM. 1987;317:141.

How Therapies Get Validated: The Evidence Hierarchy

Not all evidence is equal. Rehabilitation medicine uses a tiered evidence hierarchy to assess how confident clinicians can be in a treatment’s effects. Understanding where a therapy sits on this pyramid helps patients ask better questions and helps clinicians communicate uncertainty honestly.

Tier 1 β€” Systematic Reviews & Meta-Analyses

The gold standard. Pooled analysis of multiple RCTs. Highest confidence in effect estimates.

Tier 2 β€” Randomized Controlled Trials

Controlled experiments with random group assignment. Minimize selection bias and isolate treatment effects.

Tier 3 β€” Cohort & Case-Control Studies

Observational data. Useful for rare outcomes or long follow-up periods where RCTs are impractical.

Tier 4 β€” Case Series & Expert Opinion

Early signals. Hypothesis-generating but not confirmatory. Useful for surfacing patterns that warrant formal study.

Tier 5 β€” Preclinical / Animal / In Vitro

Mechanistic insight only. Cannot be extrapolated to clinical use without supportive human data.

Cite: Murad MH et al. New evidence pyramid. Evid Based Med. 2016;21(4):125–127.

Emerging Therapies

Seven Therapies at the Frontier of Rehabilitation Care

Each therapy below is presented with its proposed mechanism, current evidence tier, clinical applications, and known limitations. Where evidence is sparse, that is stated plainly.

1. Blood Flow Restriction Training (BFR)

Evidence Tier: 2–3 | Mechanism: Established | Clinical Use: Active

Mechanism & Evidence

BFR uses a pneumatic cuff to partially occlude venous return during low-load resistance exercise (20–40% 1RM). This creates metabolic stress and cellular swelling that stimulate muscle protein synthesis and hypertrophic signaling comparable to high-load training.

A 2019 meta-analysis (LixandrΓ£o et al., J Strength Cond Res) found BFR produced equivalent hypertrophy to traditional high-load exercise at significantly lower loads. Kilgas et al. (2019, Sports Med) demonstrated BFR efficacy in post-surgical knee rehabilitation.

Cite: LixandrΓ£o ME et al. J Strength Cond Res. 2019;33(4):1103–1113. Kilgas MA et al. Sports Med. 2019;49(7):1071–1085.

Clinical Applications & Limits

Clinical Applications

  • Post-surgical rehab (ACL, rotator cuff, hip arthroplasty)
  • Sarcopenia in older adults
  • Load-intolerant populations (osteoporosis, acute tendinopathy)

Limitations

  • Requires calibrated equipment and trained clinician
  • Contraindicated in DVT, severe peripheral arterial disease, open wounds
  • Pressure standardization across devices remains inconsistent

2. Transcranial Magnetic Stimulation & Neurostimulation

Evidence Tier: 2–3 | Mechanism: Established | Clinical Use: Active (pain/neuro)

Mechanism & Evidence

Repetitive TMS (rTMS) applies pulsed magnetic fields to the motor cortex to modulate cortical excitability. In chronic pain, it targets the primary motor cortex or dorsolateral prefrontal cortex to reduce central sensitization and alter descending pain modulation.

A 2021 Cochrane review (O’Connell et al.) found moderate-certainty evidence for rTMS reducing chronic pain intensity. Leung et al. (2020, J Pain) found significant effects on fibromyalgia and neuropathic pain.

Cite: O’Connell NE et al. Cochrane Database Syst Rev. 2021;(7):CD011080. Leung A et al. J Pain. 2020;21(7-8):796–808.

Applications & Limits

Clinical Applications

  • Chronic neuropathic pain
  • Fibromyalgia
  • Post-stroke motor rehabilitation
  • CRPS (emerging)

Limitations

  • Requires specialized equipment and trained operator
  • Effects are modest and variable across individuals
  • Not yet standard of care in most rehab settings
  • Seizure risk in susceptible individuals

3. Exosome Therapy

Evidence Tier: 4–5 | Mechanism: Plausible | Clinical Use: Investigational

Mechanism & Evidence

Exosomes are extracellular vesicles (30–150 nm) secreted by mesenchymal stem cells (MSCs) that carry bioactive cargo β€” microRNA, growth factors, proteins β€” capable of modulating inflammation, promoting angiogenesis, and stimulating tissue repair without the risks of live cell transplantation.

Preclinical data are compelling. Tao et al. (2021, Stem Cell Res Ther) showed MSC-derived exosomes accelerated cartilage repair in rat OA models. Human data remain limited to small uncontrolled series.

Cite: Tao SC et al. Stem Cell Res Ther. 2021;12(1):179. Lo Sicco C et al. Stem Cells Transl Med. 2017;6(5):1275–1286.

Applications & Limits

Potential Applications

  • Osteoarthritis (cartilage regeneration)
  • Tendon and ligament repair
  • Intervertebral disc degeneration

Limitations

  • No large-scale RCT data in humans yet
  • Standardization of exosome preparation and dosing is unresolved
  • Not FDA-cleared for orthopedic use
  • Risk of unregulated commercial offerings

4. Photobiomodulation (PBM) / Therapeutic Laser

Evidence Tier: 2–3 | Mechanism: Established | Clinical Use: Active

Photobiomodulation uses red and near-infrared light (600–1100 nm) to drive mitochondrial cytochrome c oxidase activity, increasing ATP production, reducing oxidative stress, and modulating inflammatory cytokines. High-power laser extends tissue depth penetration beyond what low-level devices achieve.

This topic is covered in full detail on our Laser Therapy page. Evidence tiers vary by condition β€” musculoskeletal pain and tendinopathy have the strongest support (Tier 2); neurological applications remain Tier 3–4.

Explore Laser Therapy β†’

5. Dry Needling & Intramuscular Stimulation (IMS)

Evidence Tier: 2–3 | Mechanism: Established | Clinical Use: Active

Mechanism & Evidence

Dry needling inserts a solid filament needle into myofascial trigger points or shortened motor endplate zones to elicit a local twitch response, reduce acetylcholine release, restore sarcomere length, and normalize dysfunctional motor unit firing.

A 2021 systematic review (Gattie et al., J Orthop Sports Phys Ther) found dry needling superior to sham for immediate pain reduction in musculoskeletal conditions. Dommerholt et al. (2019) identified central sensitization modulation as a plausible secondary mechanism.

Cite: Gattie E et al. J Orthop Sports Phys Ther. 2021;51(9):586–596. Dommerholt J et al. J Man Manip Ther. 2019;27(5):255–264.

Applications & Limits

Clinical Applications

  • Myofascial pain syndrome
  • Cervicogenic headache
  • Chronic low back pain
  • Plantar fasciitis
  • Rotator cuff dysfunction

Limitations

  • Mechanism debate continues (local vs. central effect)
  • Sham needle design makes blinding difficult
  • Variable training standards across states and professions
  • Adverse events rare but include pneumothorax (cervical/thoracic), bruising

6. Regenerative Injectables: PRP & Prolotherapy

Evidence Tier: 2–4 (varies by condition) | Mechanism: Established | Clinical Use: Active (off-label)

Mechanism & Evidence

Platelet-Rich Plasma (PRP) concentrates autologous growth factors (PDGF, TGF-Ξ², VEGF) to stimulate tendon and cartilage repair at supraphysiological levels. Prolotherapy uses hypertonic dextrose to trigger a controlled inflammatory cascade, promoting ligament and tendon regeneration.

For knee OA, a 2021 network meta-analysis (Belk et al., Am J Sports Med) found PRP superior to hyaluronic acid and corticosteroid for pain at 6 months. Tendinopathy evidence is mixed β€” lateral epicondylitis shows consistent benefit (Mishra et al., 2014); patellar tendinopathy data remain heterogeneous.

Cite: Belk JW et al. Am J Sports Med. 2021;49(13):3681–3693. Mishra AK et al. Am J Sports Med. 2014;42(2):463–471.

Applications & Limits

Clinical Applications

  • Knee osteoarthritis
  • Lateral epicondylitis (tennis elbow)
  • Patellar and Achilles tendinopathy
  • Plantar fasciitis
  • Chronic ligament laxity (prolotherapy)

Limitations

  • No FDA approval for orthopedic indications
  • Preparation protocols vary widely (centrifuge, leukocyte content, volume)
  • Insurance rarely covers β€” significant out-of-pocket cost
  • Prolotherapy RCT data thinner than PRP literature
  • Risk of post-injection flare (transient pain increase)

7. Virtual Reality (VR) Rehabilitation

Evidence Tier: 2–3 | Mechanism: Established | Clinical Use: Active (neuro/pain)

Mechanism & Evidence

VR rehabilitation uses immersive visual environments to retrain motor patterns, reduce fear-avoidance behavior, and modulate pain perception via distraction, graded motor imagery, and altered body ownership. The technology exploits neuroplasticity β€” the brain’s capacity to reorganize in response to novel sensorimotor input.

A 2022 systematic review (Laver et al., Cochrane) found moderate evidence for VR improving upper limb function post-stroke. Mallari et al. (2019, J NeuroEngineering Rehab) found VR reduced acute and chronic pain across multiple conditions. Graded exposure VR shows particular promise in CRPS and phantom limb pain.

Cite: Laver KE et al. Cochrane Database Syst Rev. 2022;(1):CD008349. Mallari B et al. J NeuroEngineering Rehab. 2019;16(1):124.

Applications & Limits

Clinical Applications

  • Post-stroke upper limb rehabilitation
  • Chronic pain (CRPS, phantom limb)
  • Fear-avoidance and kinesiophobia
  • Pediatric rehabilitation engagement
  • Balance and vestibular training

Limitations

  • Hardware cost remains a barrier in many clinics
  • Motion sickness (cybersickness) in 10–30% of users
  • Evidence base strongest for neuro; weaker for ortho MSK
  • Long-term adherence outside clinical settings largely unstudied

Responsible Innovation

How Emerging Therapies Enter Standard of Care

The path from experimental to standard care is intentional and rigorous. Understanding the stages helps patients and clinicians evaluate whether a therapy is truly ready β€” or still finding its footing.

Phase I: Safety

Small trials establish dosing, tolerability, and adverse event profiles. No efficacy claims. Most therapies never pass this point.

Phase II: Signal Detection

Larger pilot studies look for preliminary efficacy signals. Sham or active comparator groups introduced. Most evidence for emerging rehab therapies lives here.

Phase III: Confirmatory RCTs

Multicenter, adequately powered, blinded trials. The threshold for guideline inclusion. Expensive and time-consuming β€” why many promising therapies stall.

Phase IV: Post-Market Surveillance

Real-world safety and effectiveness monitoring after guideline adoption. Where rare adverse events and long-term outcomes are discovered.

Cite: ICH E8(R1) General Considerations for Clinical Studies. 2021. Freedman B. Equipoise and the ethics of clinical research. NEJM. 1987;317:141.

Evaluating Claims: Red Flags & Green Flags

Patients encounter marketing for emerging therapies long before the evidence base matures. These signals help separate responsible innovation from premature commercialization.

🚩 Red Flags

  • Guaranteed results or cure claims
  • ‘No side effects’ β€” all interventions carry risk
  • Testimonials substituting for clinical data
  • Proprietary protocols with no published research
  • Pressure to commit before consulting your provider
  • Price lists visible before any clinical assessment

βœ… Green Flags

  • Published peer-reviewed evidence cited by name
  • Honest discussion of limitations and failure rates
  • Informed consent process before treatment
  • Integration with existing care plan, not replacement
  • Clinician registered and credentialed in the modality
  • Willingness to refer out when not appropriate

The information on this page is provided for general educational purposes only and does not constitute medical advice, diagnosis, or treatment. Emerging therapies are, by definition, not yet standard of care. Clinical evidence cited reflects the state of the peer-reviewed literature at the time of publication and may have been superseded by subsequent research. Always consult a qualified healthcare provider before beginning, modifying, or discontinuing any treatment. Dr. Austin Fontenot, DC does not endorse any specific commercial product, injectable preparation, or device mentioned on this page.

Sources

References

1. Sackett DL, Rosenberg WM, Gray JA, et al. Evidence based medicine: what it is and what it isn’t. BMJ. 1996;312(7023):71–72.
2. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med. 1987;317(3):141–145.
3. Murad MH, Asi N, Alsawas M, Alahdab F. New evidence pyramid. Evid Based Med. 2016;21(4):125–127.
4. LixandrΓ£o ME, Ugrinowitsch C, Berton R, et al. Magnitude of muscle strength and mass adaptations between high-load resistance training versus low-load resistance training associated with blood-flow restriction. J Strength Cond Res. 2019;33(4):1103–1113.
5. Kilgas MA, Phillips DB, Drum SN, Elmer SJ. Exercise with blood flow restriction to rehabilitate an injury. Int J Sports Physiol Perform. 2019;14(7):871–878.
6. O’Connell NE, Marston L, Spencer S, et al. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. 2021;(7):CD011080.
7. Leung A, Donohue M, Xu R, et al. rTMS for suppressing neuropathic pain: a meta-analysis. J Pain. 2020;21(7-8):796–808.
8. Tao SC, Guo SC, Zhang CQ. Platelet-derived extracellular vesicles: an emerging therapeutic approach. Int J Biol Sci. 2021;17(2):557–568.
9. Lo Sicco C, Reverberi D, Balbi C, et al. Mesenchymal stem cell-derived extracellular vesicles as mediators of anti-inflammatory effects. Stem Cells Transl Med. 2017;6(5):1275–1286.
10. Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337–361.
11. Chung H, Dai T, Sharma SK, et al. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012;40(2):516–533.
12. Gattie E, Cleland JA, Snodgrass S. The effectiveness of trigger point dry needling for musculoskeletal conditions by physical therapists: a systematic review and meta-analysis. J Orthop Sports Phys Ther. 2021;51(9):586–596.
13. Dommerholt J, Finnegan M, Hooks T, Grieve R. A critical overview of the current myofascial pain literature. J Bodyw Mov Ther. 2019;23(3):504–516.
14. Belk JW, Kraeutler MJ, Houck DA, et al. Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2021;49(13):3681–3693.
15. Mishra AK, Skrepnik NV, Edwards SG, et al. Efficacy of platelet-rich plasma for chronic tennis elbow: a double-blind, prospective, multicenter, randomized controlled trial of 230 patients. Am J Sports Med. 2014;42(2):463–471.
16. Laver KE, Lange B, George S, et al. Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev. 2022;(1):CD008349.
17. Mallari B, Spaeth EK, Goh H, Boyd BS. Virtual reality as an analgesic for acute and chronic pain in adults: a systematic review and meta-analysis. J Pain Res. 2019;12:2243–2254.
18. ICH Expert Working Group. ICH Harmonised Guideline: General Considerations for Clinical Studies E8(R1). International Council for Harmonisation; 2021.
19. U.S. Food and Drug Administration. Platelet Rich Plasma: Fact Sheet. FDA; 2023.
20. American Physical Therapy Association. Dry Needling Position Statement. APTA; 2021.